Hypothesis of larval nutritional programming for carbohydrates utilization

2. Contents
1. Poor carbohydrates utilization in fishes and consequences in fish nutrition
2. Examples of low carbohydrates and glucose utilization in fishes
3. Several hypothesis that explain the phenomenon
4. New explanation of the phenomenon by randle’s cycle
5. New explanation of the phenomenon by glicolysis inhibition by PUFA
6. Increase glucose utilization capacity in fish by glucose early programming
7. Conclusion

4. Higher feed cost
Higher water pollution
Better carbohydrates utilization will increase
protein sparing hence it will present economical
and environmental advantages
OK !

5. The graphics show:
a. Blood glucose higher in carnivorous
than herbivorous fishes
b. Plasma insulin higher in carnivorous
than herbivorous fishes
c. Phosphofructokinase higher in herbivorous
than carnivorous fishes

6. Plasma glucose decrease below 100 mg/dl
only after 8 hours in carnivorous fish.

7. Species Carbohydrates digestion Glucose utilisation
Less ability but prefer to low amylopectin-contained
Asian seabass (Lates calcarifer) Poor (4)
and gelatinized starch (1–3)
Atlantic halibut (Hippoglossus
Less active amylase (5) Poor, but 5%-8% better than 2% (5)
hippoglossus)
Poor, but prefer to low level (<16%) (6) &
Atlantic salmon (Salmo salar) Less active amylase (6)
higher temperature (180C) (7)
Digest gelatinized starch up to 80% for <24,2% in feed
Cobia (Rachycentron canadum) Low utilized (9)
(8)
European seabass (Dicentrachus Less amylolytic activity, suggested concentration <30%
Poor (prolonged hyperglycemia) (10)
labrax) in diet (10)
Better amylolitic activity, better digest wheat and
Gilthead seabream (Sparus aurata) Restore plasma glucose after 12 h (14)
extruded source (11–13)
Prefer starch than glucose (E. malabaricus, E. coioides) Protein sparing at low protein diet (E.
Grouper
(15, 16) malabaricus) (17)
Japanese flounder (Paralichthyis
Utilize dextrin better than cellulose, maltose, glucose
olivaceus) Hyperglycemia 16-24 h (18)
(18)
Rainbow trout (Onchorynchus
Low digestible (19–21) Poor (22–25)
mykiss)
Red drum (Sciaenops ocellatus) Low digestible but prefer complex starch (26) Low utilized (26)
Red seabream (Pagrus major) Low digestible (27, 28) Low utilized compared to lipid (29, 30)
Southern bluefin tuna (Thunnus Assumed to be low digestible because low amylase
-
maccoyii) present (31–33)
Low digestible but prefer complex starch (10%-20% Low restore because low plasma insulin
Yellowtail (Seriola quinquerradiata)
diet) (34, 35) level (35)

9. Low concentration digestive enzymes (Helland and Helland, 2002)
Short gut intestine (Drew et al 2004)
Glucose low stimulate insulin secretion (Mommsen et al, 1991)
The relatively low number of insulin receptors in fish muscle as compared to the rat
(Pa´rrizas et al. 1994)
Low number of glucose transporters in fish muscle (Wright et al. 1998)
A low glucose phosphorylation capacity (Cowey and Walton 1989)
An imbalance between hepatic glucose uptake and endogenous production
(Panserat et al. 2001a)

10. Explanation for low glucose utilization by Enes et al (2009)
1. Data strongly suggest that the liver of most fish species is apparently capable of
regulating glucose storage
2. However, endogenous glucose production is still high whether fish is in feeding
or fasting state.
3. This endogenous glucose production leads a putative competition with
exogenous (dietary) glucose.
4. This may explain the poor glucose utilization in fish
(Enes et al. 2009)
But why is endogenous glucose production highly persistent ?
New explanation may be found here:
1. Gluconeogenesis could be induced by fatty acid oxidation
(Randle, 1988)
2. Fatty acid oxidation could be induced by PUFA rich diet
(Clarke, 2001)

12. Utilization of fatty acid as energy source Utilization of glucose as energy source
prevent glucose utilization prevent triacyl glycerol breakdown

17. Fatty acids that have two or more double bonds
linoleic acid (LA)
γ-linolenic acid (GLA)
arachidonic acid (AA)
Alpha-linolenic acid (ALA)
Eicosapentaenoic acid (EPA)
Docosahexaenoic acid (DHA)

18. (Delarue et al., 2004; Ghafoorunissa et al., 2005; Postic et al., 2007; Fedor and Kelley, 2009;
González-Périz et al., 2009)
PUFA Can not cure insulin resistance
Its only
Prevent insulin resistance by reduce lipid deposition
1. Decrease lipogenesis and glicolysis
2. Increase lipolysis and beta oxidation and gluconeogenesis

19. Induce fatty acid oxidation
lipolysis
glycogenesis
glucogenesis
Inhibit
lipogenesis
glycolysis
By governing
DNA binding activity
and nuclear receptors

20. PUFA PREVENT TRANSCRIPTION
BY INHIBIT ChREBP (GLYCOLISIS) AND SREBP1-C (LIPOGENESIS) (Postic et al. 2007)

22. 1. Reducing the nuclear abundance and DNA-binding affinity of transcription
factors responsible for imparting insulin and carbohydrate control to lipogenic
and glycolytic genes.
2. In particular, PUFA suppress the nuclear abundance and expression of sterol
regulatory element binding protein-1 and reduce the DNA-binding activities of
nuclear factor Y, Sp1 and possibly hepatic nuclear factor-4

23. The higher rates of fatty acid oxidation observed in humans and animals fed diets
rich in PUFA (Clark, 2001)
Oxidation of fatty acids and ketone bodies inhibit glucose metabolism in cardiac
and red skeletal muscle and induce gluconeogenesis (Randle, 1988)
Utilizing lipid simultaneously as energy source impairs insulin response by glucose
(Randle, 1998)
Fish prolonged uptake PUFA, hence simultaneously use to fatty acid as
respiratory substrates, induce gluconeogenesis finally impairs insulin
response and may have implication in metabolic inflexibility.

25. Metabolic inflexibility is simultaneously influenced by environmental condition
Carbohydrates-rich food chain Lipid-rich food chain
Glucose Lipid
Glycolisis Beta oxidation
Glycogenesis
Lipogenesis Gluconeogenesis
Natural programming

26. Nutritional programming
1. Specific fish habitat provide particular feeds that may naturally contain specific
food composition. They consume these kinds of feeds continuously.
2. Fish adapt efficiently to this condition by performing certain metabolic pathway
more often than the others. It means some genes express more frequent than
the others. Afterward , this state become fish habit.
3. It could be changed by early programming of larvae. They are conditioned
simultaneously by particular set of nutritional state that induce desired gene
expression relates to specific metabolic pathway.
4. Consequently this metabolic state is still continued in the latter of fish live stage.

27. Nutritional Programming for glucose utilization (Geurden et al 2007)
Based on the concept of nutritional programming in higher vertebrates, it was tested whether an acute hyperglucidic
stimulus during early life could induce a long-lasting effect on carbohydrate utilization in carnivorous rainbow trout.
1. hyperglucidic diet (60% dextrin) at two early stages of development: either at first feeding (3 days, stimulus 1) or
after yolk absorption (5 days, stimulus 2).
2. Before and after the hyperglucidic stimulus, they received a commercial diet until juvenile stage (>10 g).
3. Fish that did not experience the hyperglucidic stimuli served as controls.
4. The short- and long-term effects of the stimuli were evaluated by measuring the expression of five key genes
involved in carbohydrate utilization: α-amylase, maltase (digestion), sodium-dependent glucose cotransporter
(SGLT1; intestinal glucose transport), and glucokinase and glucose-6-phosphatase, involved in the utilization and
production of glucose, respectively.
5. The hyperglucidic diet rapidly increased expressions of maltase, α-amylase, and glucokinase in stimulus 1 fish and
only of maltase in stimulus 2 fish, probably because of a lower plasticity at this later stage of development.
6. In the final challenge test with juveniles fed a 25% dextrin diet, both digestive enzymes were upregulated in fish
that had experienced the hyperglucidic stimulus at first feeding, confirming the possibility of modification of some
long-term physiological functions in rainbow trout.
7. In contrast, no persistent molecular adaptations were found for the genes involved in glucose transport or
metabolism. In addition, growth and postprandial glycemia were unaffected by the stimuli.
8. In summary, data show that a short hyperglucidic stimulus during early trout life may permanently influence
carbohydrate digestion.

28. Conclusion
1. Many evidences show that fishes utilize carbohydrates and glucose poorly
2. Carnivorous fishes are lower utilize carbohydrates than the herbivorous
3. Several hypothesis that explain the phenomenon still raise many questions
4. Randle’s cycle explain more clearly that glucose utilization is inhibited by fatty acid
utilization.
5. Inhibition of glucose utilization much more plainly by glicolysis inhibition by PUFA
6. In certain level, glucose utilization capability in fish could be increased by early
programming
7. Conclusion

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