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Perinatal                  Nutrigenomics
  Nutrition, Appetite                  and
                                  Personalized

and Food Preferences                Nutrition




          Alejandra Ponce Garza
          Itxaso Vázquez Varona
DEFINITIONS

 Appetite:
   The natural instinctive desire for food.
   It should be distinguished from hunger (need for food)


 Food Preferences :
   Prefer one food to another.

 Perinatal nutrition :
   Nutrition that happens pertaining to the period immediately before and after birth
      Starts: 20 th -28 th week of gestation
      Ends: 1-4 weeks after birth.




                             Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                                         2
                              MSc. Nutrigenomics and Personalized Nutrition
BACKGROUND
1.Bellinger, Leanne, and Simon C. Langley -
Evans. "Fetal Programming of Appetite by
Exposure to Maternal Low-protein Diet in the
Rat." Clinical Science 109 (2005): 413-20. Print.
2. Brion, M.-J. A., A. R. Ness, I. Rogers, P.
Emmett, V. Cribb, G. Davey Smith, and D. A.
Lawlor. "Maternal Macronutrient and Energy
Intakes in Pregnancy and Offspring Intake at 10
Y: Exploring Parental Comparisons and Prenatal
Effects." American Journal of Clinical Nutrition
91.3 (2010): 748-56. Print.




                      Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                       3
                       MSc. Nutrigenomics and Personalized Nutrition
BACKGROUND (1)

Epidemiological observations of associations
 between early life nutrition and long-term
 disease risk have prompted detailed
 experimental investigation of the biological
 basis of programming.
  Animal experiments
  Human interventions:
      Global food restriction                                    determine a consistent
      Protein restriction                                          cluster of disorders
                                                                 in the resulting offspring
      Micronutrient restriction
      Excess fat feeding
                         Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                                          4
                          MSc. Nutrigenomics and Personalized Nutrition
BACKGROUND (2)

Maternal macronutrient (carbohydrate, fat, and protein) and
energy intakes potentially influence fetal growth and
program future appetite


Encouraging pregnant women to engage in healthy dietary
behaviors may be of benefit to the development of the fetus
and to later dietary habits of their children.




                    Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                     5
                     MSc. Nutrigenomics and Personalized Nutrition
MECHANISMS
1. Langley-Evans, Simon C., Leanne Bellinger, and
   Sarah McMullen. "Animal Models of Programming:
   Early Life Influences on Appetite and Feeding
   Behaviour." Maternal and Child Nutrition 1 (2005):
   142-48
2. Vucetic, Z., J. Kimmel, K. Totoki, E. Hollenbeck, and T.
   M. Reyes. "Maternal High-Fat Diet Alters Methylation
   and Gene Expression of Dopamine and Opioid-
   Related Genes." Endocrinology 151.10 (2010): 4756-
   764. Print
                          Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                           6
                           MSc. Nutrigenomics and Personalized Nutrition
APPETITE: MOLECULAR BASIS (1)

 Persistent hyperphagic state in animals
  exposed to:
   Fetal undernutrition
   Early postnatal overfeeding


 Non-optimal nutrition at critical phases of
  development may promote
   1. Adaptive responses
  2. Modification of the structures of key
   hypothalamic nuclei responsible for appetite
   control.
                    Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                     7
                     MSc. Nutrigenomics and Personalized Nutrition
APPETITE: MOLECULAR BASIS (1)

 Exposure of the rat fetus to
  a low protein diet modifies
  vascularization of the
  cerebral cortex.
   Bennis-Taleb et al (1999)                                Offsrping of rats fed with
                                                              low protein diet: Increased
 Rats fed low protein diets                                  neural density in the PVN
  throughout gestation and                                    and VMN, with fewer NPY
  lactation showed differences                                and CCK neurons.
  in whole brain volume and                                        Langley-Evans et al (2005)
  volume of the
  paraventricular and
  ventromedial nuclei of the
  hypothalamus.
   Plagemann et al., (2000)
                        Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                                            8
                                 MSc. Nutrigenomics and Personalized Nutrition
APPETITE.: MOLECULAR BASIS (1)

 Structural adaptations
   Permanently predispose
    the animal to increased
    appetite
 Gene microarray
  studies indicate that
  the expression of a
  relatively narrow
  profile of genes in the
  hypothalamus is
  programmed by fetal
  exposure to a maternal
  low protein diet                         Langley-Evans, Simon C., Leanne Bellinger, and Sarah McMullen. "Animal
                                           Models of Programming: Early Life Influences on Appetite and Feeding
                                           Behaviour." Maternal and Child Nutrition 1 (2005): 142-48

                     Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                                                           9
                      MSc. Nutrigenomics and Personalized Nutrition
MECHANISMS AND DNA (2)


Human study: n=4000
  Hypothesis:
   Molecules that participate in regulating consumption of
    palatable foods (dopamine and opioids) maybe altered in
    offspring from mothers fed a HF diet.
   Mechanisms: Maternal consumption of HF diet would alter
    DNA methylation either globally or within the promoter
    regions of dopamine- and opioid-related genes.
  The study examines the potential underlying
   mechanisms linking maternal consumption of HF
   diet to adverse offspring development.
                  Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                   10
                   MSc. Nutrigenomics and Personalized Nutrition
MECHANISMS AND DNA (2)

 HF diet during pregnancy and
 lactation associated with
 altered expression:
   Opioid receptor
   The opiate ligand preproenkephalin,
     Genes specifically linked to the intake
      of palatable foods.

 Epigenetic modification
  (promoter region
  hypomethylation) as a
  potential mechanism for
  increased long-term
  expression of dopamine and
  opioid-related genes
  (DAT, MOR, and PENK)                                 Vucetic, Z., J. Kimmel, K. Totoki, E. Hollenbeck, and T. M. Reyes. "Maternal High-
                                                       Fat Diet Alters Methylation and Gene Expression of Dopamine and Opioid-
                                                       Related Genes." Endocrinology 151.10 (2010): 4756-764. Print

                                Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                                                                             11
                                 MSc. Nutrigenomics and Personalized Nutrition
MECHANISMS AND DNA (2)

 Decreased methylation of the promoter region of
  GH secretagogue receptor.
   Effect persisting into at least the second generation
    suggesting the possibility that our observed epigenetic
    effects on dopamine and opioid gene expression may extend
    beyond the F1 generation.




                    Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                     12
                     MSc. Nutrigenomics and Personalized Nutrition
SALTY
1. Prenatal imprinting of postnatal specific appetites and
feeding behavior. Stylianos Nicolaïdis. Metabolism Clinical
and Experimental 57 (Suppl 2) (2008) S22–S26

2. Crystal SR, Bernstein IL. Morning sickness: impact on
offspring salt preference. Appetite 1995;25:231-40.




                        Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                         13
                         MSc. Nutrigenomics and Personalized Nutrition
APPETITE FOR SALTY (1,2)

Sodium appetite increases in response to
 hypovolemic and hypoosmotic deficits.
When these deficits recur, hypernatriophilia
 develops.
Hypernatriophilia:
  Hypothesis that extracellular dehydration imposed
   on a pregnant rat could bring about
   hypernatriophilia in its offspring when they reach
   adulthood.


                 Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                  14
                  MSc. Nutrigenomics and Personalized Nutrition
APPETITE FOR SALTY (1,2)

Hypothesis was successfully verified by
  Crystal and Bernstein
   cohort of 169 students: reported higher salt use were
    precisely the ones whose mothers had experienced
    vomiting during pregnancy.
  Kochli and coworkers.
  Curtis and associates have shown in the rat that
   manipulations of dietary NaCl levels during
   gestation and the early postnatal period lead to
   persistent changes both in “need-free” and
   stimulated NaCl intake by adult rats.
                   Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                    15
                    MSc. Nutrigenomics and Personalized Nutrition
FLAVORS
1. Trout, K. K., and L. Wetzel -Effinger. "Flavor
Learning in Utero and Its Implicat ions for Future
Obesity and Diabetes." Current Diabetes Reports 12.1
(2012): 60+. Print.
2. Mennella, J. A., C. P. Jagnow, and G. K. Beauchamp.
"Prenatal and Postnatal Flavor Learning by Human
Infants." Pediatrics 107.6 (2001): E88
3. Mannella, J. A., C. E. Griffi n, and G. K. Beauchamp.
"Flavor Programming During Infanc y." Pediatrics 113.4
(2004): 840-45. Print.




                          Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                           16
                           MSc. Nutrigenomics and Personalized Nutrition
FLAVORS (1,3)

Flavors in the mother diet  Amniotic fluid.
  Amniotic fluid swallowed by the fetus.
  PREFERENCES.
  Persisten during infancy Childhood  Adulthood


Early exposure to different flavors can lead
 to increased acceptance of and preferences
 for these flavors in later life.


                Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                 17
                 MSc. Nutrigenomics and Personalized Nutrition
FLAVORS (3)

 Hydrolyzed
  protein formulas.




                                 Mannella, J. A., C. E. Griffin, and G. K. Beauchamp. "Flavor Programming During
                                 Infancy." Pediatrics 113.4 (2004): 840-45. Print.
                  Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                                                             18
                   MSc. Nutrigenomics and Personalized Nutrition
FLAVORS (2)

 First experimental study that demonstrates that
  prenatal flavor experiences enhances the
  acceptances and enjoyment of similarly flavored
  foods during weaning.
 Groups: 46 women. Drank  300ml
                        Pregnancy                Lactation
           1 - CW       Carrot Juice             Water
           2 - WC       Water                    Carrot Juice
           3 - WW       Water                    Water

 Babies: CW  weaning period  enjoyment of
 carrot-flavored cereal.
                    Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                     19
                     MSc. Nutrigenomics and Personalized Nutrition
JUNK FOOD
1. Bayol, Stéphanie A., Samantha J. Farrington, and
Neil C. Stickland. "A Maternal ‘junk Food’ Diet in
Pregnancy and Lactation Promotes an Exacerbated
Taste for ‘junk Food’ and a Greater Propensity for
Obesity in Rat Offspring." British Journal of Nutrition
98.04 (2007). Print.




                          Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                           20
                           MSc. Nutrigenomics and Personalized Nutrition
JUNK FOOD (1)




Bayol, Stéphanie A., Samantha J. Farrington, and Neil C. Stickland. "A Maternal ‘junk Food’ Diet in Pregnancy
and Lactation Promotes an Exacerbated Taste for ‘junk Food’ and a Greater Propensity for Obesity in Rat
Offspring." British Journal of Nutrition 98.04 (2007). Print

                              Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                                                                21
                               MSc. Nutrigenomics and Personalized Nutrition
 A maternal junk food diet before weaning
       promotes an exacerbated preference for junk
       food and leads to a greater propensity for
       obesity in the offspring.
         Palatability
         Protection against hyperphagia when mother
          was fed –at some point- with a control diet.

                                                                                                                              JUNK
                                                                                                              JJJ
                                                                                                                              FOOD
                                                                                                                      CCJ
                                                                                                                               (1)
                                                                                                                      JCJ

                                                                                             CCC         JJC        JCC




Bayol, Stéphanie A., Samantha J. Farrington, and Neil C. Stickland. "A Maternal ‘junk Food’ Diet in Pregnancy and Lactation
Promotes an Exacerbated Taste for ‘junk Food’ and a Greater Propensity for Obesity in Rat Offspring." British Journal of
Nutrition 98.04 (2007). Print
                                                           Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                                                                                 22
                                                            MSc. Nutrigenomics and Personalized Nutrition
JUNK FOOD (1)

Palatability
  Major role in
   appetite regulation.
  Inhibit the satiety
   signal while
   promoting hunger
   and stimulating the
   reward centres.

                                Bayol, Stéphanie A., Samantha J. Farrington, and Neil C. Stickland. "A Maternal ‘junk
                                Food’ Diet in Pregnancy and Lactation Promotes an Exacerbated Taste for ‘junk Food’
                                and a Greater Propensity for Obesity in Rat Offspring." British Journal of Nutrition
                                98.04 (2007). Print


                    Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                                                                23
                     MSc. Nutrigenomics and Personalized Nutrition
JUNK FOOD (1)

 Lactation: important
  period for the
  programming of an
  exacerbated intake of
  junk food.
  Key role in influencing
   long-term appetite.
  Milk intake and
   composition might be key
   regulators of the
   development and
   maturation of the central             Bayol, Stéphanie A., Samantha J. Farrington, and Neil C. Stickland. "A
                                         Maternal ‘junk Food’ Diet in Pregnancy and Lactation Promotes an
   and peripheral control of             Exacerbated Taste for ‘junk Food’ and a Greater Propensity for Obesity in
   appetite.                             Rat Offspring." British Journal of Nutrition 98.04 (2007). Print




                    Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                                                               24
                     MSc. Nutrigenomics and Personalized Nutrition
PALATABILITY
1. Langley-Evans , Simon C., Leanne Bellinger, and
   Sarah McMullen . "Animal Models of Programming:
   Early Life Influences on Appetite and Feeding
   Behaviour." Maternal and Child Nutrition 1 (2005):
   142-48
2. Vucetic , Z., J. Kimmel, K. Totoki, E. Hollenbeck, and
   T. M. Reyes. "Maternal High -Fat Diet Alters
   Methylation and Gene Expression of Dopamine and
   Opioid-Related Genes." Endocrinology 151.10
   (2010): 4756-764. Print
3. Teegarden , S.l., A.n. Scott, and T.l. Bale. "Early Life
   Exposure to a High Fat Diet Promotes Long -ter m
   Changes in Dietary Preferences and Central Reward
   Signaling." Neuroscience 162.4 (2009): 924-32. Print




                           Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                            25
                            MSc. Nutrigenomics and Personalized Nutrition
HIGH-FAT FOOD (1)

 First evidence of
  perturbation of the
  nutritional
  environment in utero:
  12 week old female
   offspring of rats fed with
   low-protein diet during
   gestation and lactation
   preferred a high-fat diet
   over a high-protein or a
   high-carbohydrate diet.            Langley-Evans, Simon C., Leanne Bellinger, and Sarah McMullen. "Animal Models
                                      of Programming: Early Life Influences on Appetite and Feeding Behaviour."
                                      Maternal and Child Nutrition 1 (2005): 142-48


                      Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                                                           26
                       MSc. Nutrigenomics and Personalized Nutrition
HIGH-FAT AND HIGH-
        CARBOHYDRATE FOOD (2)
 Effect of HF diet and/or maternal obesity on
  hypothalamic neuropeptides that affect food intake
   Increased expression of NPY, AgRP, NPY Y1 receptor, and
    MC4Rand, more consistently, an increase in POMC.
   Increase neurogenesis, specifically neurons that express
    galanin, enkephalin, dynorphin, orexin, and MCH
   Differential expression of dopamine- related genes in the
    nucleus accumbens (NAc).
   Little examination of circuitry outside the hypothalamus
 Animal studies have shown that maternal
  consumption of a palatable diet can increase the
  preference for fat and sugar in the offspring
                     Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                      27
                      MSc. Nutrigenomics and Personalized Nutrition
HIGH-FAT AND HIGH-
          CARBOHYDRATE FOOD (3)
 Examination of the effects of early life exposure to
  a high fat diet on adult macronutrient preferences
  in mice:
 Mice were exposed to a high fat diet for one week, from postnatal days
 21-28:
  The time during which they begin to consume solid food and are no
   longer dependent on the dam for nutrition
  Hypothalamic development is complete,


 In a 10-day macronutrient choice preference test, high fat diet early -
 exposed mice showed
  A significantl y greater preferenc e for a high fat diet as adults
  No differenc es in total daily caloric intake or weight gain during the
   macronutrient choice preference period

                          Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                             28
                           MSc. Nutrigenomics and Personalized Nutrition
HIGH-FAT AND HIGH-
      CARBOHYDRATE FOOD (3)

Possible mechanisms:
  Reduced dopamine signal transmission in the
   ventral striatum in these mice may result in an
   increased preference for the high fat diet in an
   attempt to normalize dopamine levels.
  Exposure to a palatable, high fat diet during early
   life may lead to long-term reprogramming of the
   reward system,
    Risk for maladaptive eating habits
    Risk for disorders of the reward system.

                   Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                    29
                    MSc. Nutrigenomics and Personalized Nutrition
CONTRADICTION
1. Bellinger, Leanne, and Simon C. Langley -
Evans. "Fetal Programming of Appetite by
Exposure to Maternal Low -protein Diet in the
Rat." Clinical Science 109 (2005): 413-20.
Print.




                     Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                      30
                      MSc. Nutrigenomics and Personalized Nutrition
LOW-PROTEIN  HIGH-FAT FOOD (1)

 Low protein diets:
   LP-Early: 0-7 day of gestation
   LP-Medium: 8-14 day gestation
   LP-Late: 15-22 day of gestation
 At 4 weeks of age: offspring
  were weaned on to standard
  chow diet.
 At 12 weeks of age, two
  male and two female
  offspring from each litter
  were self-selection diet
  protocol to assess appetite
  and food preferences.
                                                 Bellinger, Leanne, and Simon C. Langley-Evans. "Fetal Programming of
                                                 Appetite by Exposure to Maternal Low-protein Diet in the Rat." Clinical
                                                 Science 109 (2005): 413-20. Print.

                        Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                                                                   31
                         MSc. Nutrigenomics and Personalized Nutrition
FUTURE PERSPECTIVES

 Guidelines for nutrition during pregnancy and
  lactation  Flavors.
 Infant formulas  Flavors
 Investigate more about mechanisms.




                  Itxaso Vázquez Varona * Alejandra Ponce Garza
                                                                   32
                   MSc. Nutrigenomics and Personalized Nutrition

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Perinatal Nutrition, Appetite And Food Preferences

  • 1. Perinatal Nutrigenomics Nutrition, Appetite and Personalized and Food Preferences Nutrition Alejandra Ponce Garza Itxaso Vázquez Varona
  • 2. DEFINITIONS  Appetite:  The natural instinctive desire for food.  It should be distinguished from hunger (need for food)  Food Preferences :  Prefer one food to another.  Perinatal nutrition :  Nutrition that happens pertaining to the period immediately before and after birth  Starts: 20 th -28 th week of gestation  Ends: 1-4 weeks after birth. Itxaso Vázquez Varona * Alejandra Ponce Garza 2 MSc. Nutrigenomics and Personalized Nutrition
  • 3. BACKGROUND 1.Bellinger, Leanne, and Simon C. Langley - Evans. "Fetal Programming of Appetite by Exposure to Maternal Low-protein Diet in the Rat." Clinical Science 109 (2005): 413-20. Print. 2. Brion, M.-J. A., A. R. Ness, I. Rogers, P. Emmett, V. Cribb, G. Davey Smith, and D. A. Lawlor. "Maternal Macronutrient and Energy Intakes in Pregnancy and Offspring Intake at 10 Y: Exploring Parental Comparisons and Prenatal Effects." American Journal of Clinical Nutrition 91.3 (2010): 748-56. Print. Itxaso Vázquez Varona * Alejandra Ponce Garza 3 MSc. Nutrigenomics and Personalized Nutrition
  • 4. BACKGROUND (1) Epidemiological observations of associations between early life nutrition and long-term disease risk have prompted detailed experimental investigation of the biological basis of programming.  Animal experiments  Human interventions:  Global food restriction determine a consistent  Protein restriction cluster of disorders in the resulting offspring  Micronutrient restriction  Excess fat feeding Itxaso Vázquez Varona * Alejandra Ponce Garza 4 MSc. Nutrigenomics and Personalized Nutrition
  • 5. BACKGROUND (2) Maternal macronutrient (carbohydrate, fat, and protein) and energy intakes potentially influence fetal growth and program future appetite Encouraging pregnant women to engage in healthy dietary behaviors may be of benefit to the development of the fetus and to later dietary habits of their children. Itxaso Vázquez Varona * Alejandra Ponce Garza 5 MSc. Nutrigenomics and Personalized Nutrition
  • 6. MECHANISMS 1. Langley-Evans, Simon C., Leanne Bellinger, and Sarah McMullen. "Animal Models of Programming: Early Life Influences on Appetite and Feeding Behaviour." Maternal and Child Nutrition 1 (2005): 142-48 2. Vucetic, Z., J. Kimmel, K. Totoki, E. Hollenbeck, and T. M. Reyes. "Maternal High-Fat Diet Alters Methylation and Gene Expression of Dopamine and Opioid- Related Genes." Endocrinology 151.10 (2010): 4756- 764. Print Itxaso Vázquez Varona * Alejandra Ponce Garza 6 MSc. Nutrigenomics and Personalized Nutrition
  • 7. APPETITE: MOLECULAR BASIS (1)  Persistent hyperphagic state in animals exposed to:  Fetal undernutrition  Early postnatal overfeeding  Non-optimal nutrition at critical phases of development may promote  1. Adaptive responses 2. Modification of the structures of key hypothalamic nuclei responsible for appetite control. Itxaso Vázquez Varona * Alejandra Ponce Garza 7 MSc. Nutrigenomics and Personalized Nutrition
  • 8. APPETITE: MOLECULAR BASIS (1)  Exposure of the rat fetus to a low protein diet modifies vascularization of the cerebral cortex.  Bennis-Taleb et al (1999)  Offsrping of rats fed with low protein diet: Increased  Rats fed low protein diets neural density in the PVN throughout gestation and and VMN, with fewer NPY lactation showed differences and CCK neurons. in whole brain volume and  Langley-Evans et al (2005) volume of the paraventricular and ventromedial nuclei of the hypothalamus.  Plagemann et al., (2000) Itxaso Vázquez Varona * Alejandra Ponce Garza 8 MSc. Nutrigenomics and Personalized Nutrition
  • 9. APPETITE.: MOLECULAR BASIS (1)  Structural adaptations  Permanently predispose the animal to increased appetite  Gene microarray studies indicate that the expression of a relatively narrow profile of genes in the hypothalamus is programmed by fetal exposure to a maternal low protein diet Langley-Evans, Simon C., Leanne Bellinger, and Sarah McMullen. "Animal Models of Programming: Early Life Influences on Appetite and Feeding Behaviour." Maternal and Child Nutrition 1 (2005): 142-48 Itxaso Vázquez Varona * Alejandra Ponce Garza 9 MSc. Nutrigenomics and Personalized Nutrition
  • 10. MECHANISMS AND DNA (2) Human study: n=4000  Hypothesis:  Molecules that participate in regulating consumption of palatable foods (dopamine and opioids) maybe altered in offspring from mothers fed a HF diet.  Mechanisms: Maternal consumption of HF diet would alter DNA methylation either globally or within the promoter regions of dopamine- and opioid-related genes.  The study examines the potential underlying mechanisms linking maternal consumption of HF diet to adverse offspring development. Itxaso Vázquez Varona * Alejandra Ponce Garza 10 MSc. Nutrigenomics and Personalized Nutrition
  • 11. MECHANISMS AND DNA (2)  HF diet during pregnancy and lactation associated with altered expression:  Opioid receptor  The opiate ligand preproenkephalin,  Genes specifically linked to the intake of palatable foods.  Epigenetic modification (promoter region hypomethylation) as a potential mechanism for increased long-term expression of dopamine and opioid-related genes (DAT, MOR, and PENK) Vucetic, Z., J. Kimmel, K. Totoki, E. Hollenbeck, and T. M. Reyes. "Maternal High- Fat Diet Alters Methylation and Gene Expression of Dopamine and Opioid- Related Genes." Endocrinology 151.10 (2010): 4756-764. Print Itxaso Vázquez Varona * Alejandra Ponce Garza 11 MSc. Nutrigenomics and Personalized Nutrition
  • 12. MECHANISMS AND DNA (2)  Decreased methylation of the promoter region of GH secretagogue receptor.  Effect persisting into at least the second generation suggesting the possibility that our observed epigenetic effects on dopamine and opioid gene expression may extend beyond the F1 generation. Itxaso Vázquez Varona * Alejandra Ponce Garza 12 MSc. Nutrigenomics and Personalized Nutrition
  • 13. SALTY 1. Prenatal imprinting of postnatal specific appetites and feeding behavior. Stylianos Nicolaïdis. Metabolism Clinical and Experimental 57 (Suppl 2) (2008) S22–S26 2. Crystal SR, Bernstein IL. Morning sickness: impact on offspring salt preference. Appetite 1995;25:231-40. Itxaso Vázquez Varona * Alejandra Ponce Garza 13 MSc. Nutrigenomics and Personalized Nutrition
  • 14. APPETITE FOR SALTY (1,2) Sodium appetite increases in response to hypovolemic and hypoosmotic deficits. When these deficits recur, hypernatriophilia develops. Hypernatriophilia:  Hypothesis that extracellular dehydration imposed on a pregnant rat could bring about hypernatriophilia in its offspring when they reach adulthood. Itxaso Vázquez Varona * Alejandra Ponce Garza 14 MSc. Nutrigenomics and Personalized Nutrition
  • 15. APPETITE FOR SALTY (1,2) Hypothesis was successfully verified by  Crystal and Bernstein  cohort of 169 students: reported higher salt use were precisely the ones whose mothers had experienced vomiting during pregnancy.  Kochli and coworkers.  Curtis and associates have shown in the rat that manipulations of dietary NaCl levels during gestation and the early postnatal period lead to persistent changes both in “need-free” and stimulated NaCl intake by adult rats. Itxaso Vázquez Varona * Alejandra Ponce Garza 15 MSc. Nutrigenomics and Personalized Nutrition
  • 16. FLAVORS 1. Trout, K. K., and L. Wetzel -Effinger. "Flavor Learning in Utero and Its Implicat ions for Future Obesity and Diabetes." Current Diabetes Reports 12.1 (2012): 60+. Print. 2. Mennella, J. A., C. P. Jagnow, and G. K. Beauchamp. "Prenatal and Postnatal Flavor Learning by Human Infants." Pediatrics 107.6 (2001): E88 3. Mannella, J. A., C. E. Griffi n, and G. K. Beauchamp. "Flavor Programming During Infanc y." Pediatrics 113.4 (2004): 840-45. Print. Itxaso Vázquez Varona * Alejandra Ponce Garza 16 MSc. Nutrigenomics and Personalized Nutrition
  • 17. FLAVORS (1,3) Flavors in the mother diet  Amniotic fluid.  Amniotic fluid swallowed by the fetus.  PREFERENCES.  Persisten during infancy Childhood  Adulthood Early exposure to different flavors can lead to increased acceptance of and preferences for these flavors in later life. Itxaso Vázquez Varona * Alejandra Ponce Garza 17 MSc. Nutrigenomics and Personalized Nutrition
  • 18. FLAVORS (3)  Hydrolyzed protein formulas. Mannella, J. A., C. E. Griffin, and G. K. Beauchamp. "Flavor Programming During Infancy." Pediatrics 113.4 (2004): 840-45. Print. Itxaso Vázquez Varona * Alejandra Ponce Garza 18 MSc. Nutrigenomics and Personalized Nutrition
  • 19. FLAVORS (2)  First experimental study that demonstrates that prenatal flavor experiences enhances the acceptances and enjoyment of similarly flavored foods during weaning.  Groups: 46 women. Drank  300ml Pregnancy Lactation 1 - CW Carrot Juice Water 2 - WC Water Carrot Juice 3 - WW Water Water  Babies: CW  weaning period  enjoyment of carrot-flavored cereal. Itxaso Vázquez Varona * Alejandra Ponce Garza 19 MSc. Nutrigenomics and Personalized Nutrition
  • 20. JUNK FOOD 1. Bayol, Stéphanie A., Samantha J. Farrington, and Neil C. Stickland. "A Maternal ‘junk Food’ Diet in Pregnancy and Lactation Promotes an Exacerbated Taste for ‘junk Food’ and a Greater Propensity for Obesity in Rat Offspring." British Journal of Nutrition 98.04 (2007). Print. Itxaso Vázquez Varona * Alejandra Ponce Garza 20 MSc. Nutrigenomics and Personalized Nutrition
  • 21. JUNK FOOD (1) Bayol, Stéphanie A., Samantha J. Farrington, and Neil C. Stickland. "A Maternal ‘junk Food’ Diet in Pregnancy and Lactation Promotes an Exacerbated Taste for ‘junk Food’ and a Greater Propensity for Obesity in Rat Offspring." British Journal of Nutrition 98.04 (2007). Print Itxaso Vázquez Varona * Alejandra Ponce Garza 21 MSc. Nutrigenomics and Personalized Nutrition
  • 22.  A maternal junk food diet before weaning promotes an exacerbated preference for junk food and leads to a greater propensity for obesity in the offspring.  Palatability  Protection against hyperphagia when mother was fed –at some point- with a control diet. JUNK JJJ FOOD CCJ (1) JCJ CCC JJC JCC Bayol, Stéphanie A., Samantha J. Farrington, and Neil C. Stickland. "A Maternal ‘junk Food’ Diet in Pregnancy and Lactation Promotes an Exacerbated Taste for ‘junk Food’ and a Greater Propensity for Obesity in Rat Offspring." British Journal of Nutrition 98.04 (2007). Print Itxaso Vázquez Varona * Alejandra Ponce Garza 22 MSc. Nutrigenomics and Personalized Nutrition
  • 23. JUNK FOOD (1) Palatability  Major role in appetite regulation.  Inhibit the satiety signal while promoting hunger and stimulating the reward centres. Bayol, Stéphanie A., Samantha J. Farrington, and Neil C. Stickland. "A Maternal ‘junk Food’ Diet in Pregnancy and Lactation Promotes an Exacerbated Taste for ‘junk Food’ and a Greater Propensity for Obesity in Rat Offspring." British Journal of Nutrition 98.04 (2007). Print Itxaso Vázquez Varona * Alejandra Ponce Garza 23 MSc. Nutrigenomics and Personalized Nutrition
  • 24. JUNK FOOD (1)  Lactation: important period for the programming of an exacerbated intake of junk food.  Key role in influencing long-term appetite.  Milk intake and composition might be key regulators of the development and maturation of the central Bayol, Stéphanie A., Samantha J. Farrington, and Neil C. Stickland. "A Maternal ‘junk Food’ Diet in Pregnancy and Lactation Promotes an and peripheral control of Exacerbated Taste for ‘junk Food’ and a Greater Propensity for Obesity in appetite. Rat Offspring." British Journal of Nutrition 98.04 (2007). Print Itxaso Vázquez Varona * Alejandra Ponce Garza 24 MSc. Nutrigenomics and Personalized Nutrition
  • 25. PALATABILITY 1. Langley-Evans , Simon C., Leanne Bellinger, and Sarah McMullen . "Animal Models of Programming: Early Life Influences on Appetite and Feeding Behaviour." Maternal and Child Nutrition 1 (2005): 142-48 2. Vucetic , Z., J. Kimmel, K. Totoki, E. Hollenbeck, and T. M. Reyes. "Maternal High -Fat Diet Alters Methylation and Gene Expression of Dopamine and Opioid-Related Genes." Endocrinology 151.10 (2010): 4756-764. Print 3. Teegarden , S.l., A.n. Scott, and T.l. Bale. "Early Life Exposure to a High Fat Diet Promotes Long -ter m Changes in Dietary Preferences and Central Reward Signaling." Neuroscience 162.4 (2009): 924-32. Print Itxaso Vázquez Varona * Alejandra Ponce Garza 25 MSc. Nutrigenomics and Personalized Nutrition
  • 26. HIGH-FAT FOOD (1)  First evidence of perturbation of the nutritional environment in utero:  12 week old female offspring of rats fed with low-protein diet during gestation and lactation preferred a high-fat diet over a high-protein or a high-carbohydrate diet. Langley-Evans, Simon C., Leanne Bellinger, and Sarah McMullen. "Animal Models of Programming: Early Life Influences on Appetite and Feeding Behaviour." Maternal and Child Nutrition 1 (2005): 142-48 Itxaso Vázquez Varona * Alejandra Ponce Garza 26 MSc. Nutrigenomics and Personalized Nutrition
  • 27. HIGH-FAT AND HIGH- CARBOHYDRATE FOOD (2)  Effect of HF diet and/or maternal obesity on hypothalamic neuropeptides that affect food intake  Increased expression of NPY, AgRP, NPY Y1 receptor, and MC4Rand, more consistently, an increase in POMC.  Increase neurogenesis, specifically neurons that express galanin, enkephalin, dynorphin, orexin, and MCH  Differential expression of dopamine- related genes in the nucleus accumbens (NAc).  Little examination of circuitry outside the hypothalamus  Animal studies have shown that maternal consumption of a palatable diet can increase the preference for fat and sugar in the offspring Itxaso Vázquez Varona * Alejandra Ponce Garza 27 MSc. Nutrigenomics and Personalized Nutrition
  • 28. HIGH-FAT AND HIGH- CARBOHYDRATE FOOD (3)  Examination of the effects of early life exposure to a high fat diet on adult macronutrient preferences in mice: Mice were exposed to a high fat diet for one week, from postnatal days 21-28:  The time during which they begin to consume solid food and are no longer dependent on the dam for nutrition  Hypothalamic development is complete, In a 10-day macronutrient choice preference test, high fat diet early - exposed mice showed  A significantl y greater preferenc e for a high fat diet as adults  No differenc es in total daily caloric intake or weight gain during the macronutrient choice preference period Itxaso Vázquez Varona * Alejandra Ponce Garza 28 MSc. Nutrigenomics and Personalized Nutrition
  • 29. HIGH-FAT AND HIGH- CARBOHYDRATE FOOD (3) Possible mechanisms:  Reduced dopamine signal transmission in the ventral striatum in these mice may result in an increased preference for the high fat diet in an attempt to normalize dopamine levels.  Exposure to a palatable, high fat diet during early life may lead to long-term reprogramming of the reward system,  Risk for maladaptive eating habits  Risk for disorders of the reward system. Itxaso Vázquez Varona * Alejandra Ponce Garza 29 MSc. Nutrigenomics and Personalized Nutrition
  • 30. CONTRADICTION 1. Bellinger, Leanne, and Simon C. Langley - Evans. "Fetal Programming of Appetite by Exposure to Maternal Low -protein Diet in the Rat." Clinical Science 109 (2005): 413-20. Print. Itxaso Vázquez Varona * Alejandra Ponce Garza 30 MSc. Nutrigenomics and Personalized Nutrition
  • 31. LOW-PROTEIN  HIGH-FAT FOOD (1)  Low protein diets:  LP-Early: 0-7 day of gestation  LP-Medium: 8-14 day gestation  LP-Late: 15-22 day of gestation  At 4 weeks of age: offspring were weaned on to standard chow diet.  At 12 weeks of age, two male and two female offspring from each litter were self-selection diet protocol to assess appetite and food preferences. Bellinger, Leanne, and Simon C. Langley-Evans. "Fetal Programming of Appetite by Exposure to Maternal Low-protein Diet in the Rat." Clinical Science 109 (2005): 413-20. Print. Itxaso Vázquez Varona * Alejandra Ponce Garza 31 MSc. Nutrigenomics and Personalized Nutrition
  • 32. FUTURE PERSPECTIVES  Guidelines for nutrition during pregnancy and lactation  Flavors.  Infant formulas  Flavors  Investigate more about mechanisms. Itxaso Vázquez Varona * Alejandra Ponce Garza 32 MSc. Nutrigenomics and Personalized Nutrition