The document discusses fat tissue and obesity, defining obesity, examining fat distribution and the functions of adipose tissue, and exploring the brain-gut pathways that regulate appetite and fat mass, concluding that excess dietary fat intake can harm metabolic health by damaging adipose tissue.
1. Fat – good or bad?
Dr. Katarina Kos
Senior Clinical Lecturer
Obesity Lead, RD&E
Exeter
June 2012
2. Overview
• What is the definition of obesity and
fatness?
• Fat tissue health
• Regulation of appetite and adipose tissue
mass: the brain-gut-fat axis
5. Definition of obesity
• Body Mass Index: Body weight (kg)/ height
squared (m2)
Category (adults) BMI range (kg/m2)
UNDERWEIGHT <18.5
NORMAL 18.5-24.9
OVERWEIGHT 25-29.9
OBESE >30
MORBIDLY OBESE >40
Obesity is an accumulation of fat mass, which is clinically
difficult to measure and standardise
6. Determination of ‘fatness’
• Waist circumference (cm)
Men Women
Low <94 <80
High 94-102 80-88
Very high >102 >88
• Waist-to-hip ratio
• Skinfold thickness (biceps, triceps,
subscapular)
• Fat mass (DXA scan, MRI scan or
Bodpod)
7. Adipose tissue distribution
upper body distribution : android, male, central, upper-
body segment, or "apple"
lower body fat distribution: gynoid, female, lower-
body segment , or "pear“ shape
What factors determine fat distribution?
◦ Ethnic background
◦ Gender
◦ Age
8. Function of adipose tissue
•Storage of triglycerides-
surplus energy
•Insulation
•Endocrine:
• appetite
• immunregulation
•Autocrine/paracrine:
• immunregulation White versus brown fat
• FFA regulation:
lipogenesis and lipolysis
9. Action of insulin on adipose tissue
Increased FFA
deposition with Insulin
20. Modified from Hegele et al, J Lipid Research, 2007
Congenital Familial Acquired LD HIV-
LD partial LD related
HAART-
Age at onset birth puberty <20 years induced
any
BMI normal or ↓ normal to ↑ normal to ↑ normal
Genes CGL1(AGPTAT2),CGLT FPLD2(LMNA), FPlD3 --- ---
2 (BSCL2) (PPARG)
CAV1 Akt 2
ZIMPSE24
Gluteal fat ↓↓↓ ↓↓ ↓ to ↑ 0-↓
Limb fat ↓↓↓ ↓↓↓ ↓↓ 0-↓↓
Trunk fat ↓↓↓ ↑↑↑ 0-↓↓ ↑↑-↓↓
Hepatosteato present possible In generalized LD possible
sis
Diabetes Very common Depending on In generalized LD Common
mutation
Acanthosis present present possible rare
nigricans
Other Hirsutism, bone
cysts. CGLT2:
--- Autoimmune disorders,
low C3,
--
Features mental retardation, membranoproliferative
cardiomyopathy glomerolunephritis
24. 'Good' baby fat keeps adults slim
Adults who retain their 'good' baby fat may be buffered against obesity and type 2
diabetes, scientists believe.
Unlike the regular white fat, which stores energy, good brown fat, actively burns calories for heat,
but has been thought only to exist in childhood.
Researchers at the Joslin Diabetes Center not only found adults still had brown fat, but that slim
adults had more of it than fatter ones.
Women appear to have more
'good' brown fat
36. Gut hormones: Ghrelin
Effects of three types of macronutrient
ingestion on plasma acyl-ghrelin (A) and
total ghrelin (B) levels expressed as a
percentage of their respective baseline
37.
38. GLP-1
What do you know about GLP-1
metabolism?
GLP-1 receptor in adipose tissue
GLP-1 enhances adipogenesis
people with higher expression have done better after
bariatric surgery ( Vendrell J, Endocrinology 2011)
39. DPP-IV and fat tissue
Why are DPP-IV inhibitors
weight neutral?
Kos K, Diabetes, Obesity and Metabolism, 2009
40. DPP-IV expression in abdominal Sc tissue
250
DPP IV mRNA expression in SU
200
150
*
100
50
0
Sc Sc
Lean Obese
41.
42. Summary
Fat tissue is not to be mistaken by surplus
lipids
Adipose tissue is to compensate for
lipotoxicity
Dietary surplus of FA is detrimental to
metabolic health
Adipose tissue a victim of overeating
‘Not glamorous but essential’
43. When picking up his take away pizza:
"You better cut the pizza in four pieces
because I'm not hungry enough to eat six.“
Yogi Berra
Notas do Editor
BMI acts as an index of body fat mass - not perfect, but - easy to measure and - correlates well with health outcomes
Differences in men and women
after the menopause a change towards upper body fat distribution is observed. This change may be due to a relative decrease in LPL activity in the lower body region
TG in the chylomicrons are broken down by lipoprotein lipase releasing free fatty acids (FFA) for use in energy production or for storage in the fat cells as TG Cholesteryl ester transfer protein (CETP) is a glycoprotein that is secreted mainly by the liver. CETP circulates in the plasma bound to lipoproteins, mainly high-density lipoproteins (HDL). CETP has a role in the transfer of TG in the chylomicrons to HDL in exchange for CE. This leads to the formation of chylomicron remnants, which are normally rapidly cleared from the plasma The fat is usually dissolved in routine sections, leaving a large, empty vacuole. The loss of lipid leads to a &quot;chicken wire&quot; appearance. However, the fat can be stained by special procedures using Sudan black, Sudan red (right panel), or osmic acid. Fat cells appear round when they are present singly or in small groups. In large masses, their shapes are deformed due to mutual pressure. The precursors of adipocytes resemble fibroblasts and are derived from mesenchymal cells. During development and during refeeding after a fast or weight loss, mature fat cells accumulate small lipid inclusions, which then form larger, but still numerous inclusions. These further coalesce until a large, single lipid droplet occupies almost the entire cell. The size of the cell also increases during this process. The fat content is not static; it is continually mobilized and reformed by the processes of lipolysis and lipogenesis. With weight loss, fat cells of white adipose tissue can revert to a precursor form, but retain the potential to again become active fat cells. Thus, the cells become smaller, contain less lipid, but are not lost.
Facial fat loss in congenital form; Prevalence: LMNA prone to early CVD, hypertension common in familal
responses to food intake and food cues, dopamine function and brain volume in lean vs. obese individuals are now beginning to coalesce in identifying irregularities in a range of regions implicated in reward (e.g. striatum, orbitofrontal cortex, insula), emotion and memory (e.g. amygdala, hippocampus), homeostatic regulation of intake (e.g. hypothalamus), sensory and motor processing (e.g. insula, precentral gyrus), and cognitive control and attention (e.g. prefrontal Cortex, cingulate). F MRI local neuronal activity from blood-oxygen-level dependent changes in the paramagnetic properties of haemoglobin.
Lipocentric model
Triglycerides may modify blood brain barrier function and inhibit leptin transport Resistance is associated with impaired transporter, receptor, postreceptor, and downstream neuronal circuitry functions in animal models of obesity (9 –13). Leptin is transported across the blood-brain barrier (BBB) by a saturable transporter (8), and impaired transport can be acquired, may precede receptor/postreceptor defects, worsens with increasing obesity, and is to some extent reversible (14 –16). The relation between cerebrospinal fluid and serum levels of leptin in obese humans (17,18) suggests that defective BBB transport accounts for more of the overall resistance to leptin than the receptor/postreceptor defects (19). The obesity-related defect in leptin BBB transport has two aspects (10). First, circulating substances cause an immediate impairment. Leptin itself, which is elevated in obesity, is likely one of these circulating substances. Second, an unidentified mechanism impairs transport in obese mice even when BBB transport is assessed by brain perfusion, a method that removes the immediate effects of blood-borne substances. Fasting or leptin administration can partially reverse these defects in leptin transport (16). Starvation, like obesity, is accompanied by a decreased BBB transport rate of exogenous leptin (20). Whereas it is difficult to explain the evolutionary advantage of decreased leptin transport in obesity, an advantage is obvious in starvation. Decreasing the amount of the anorectic protein reaching the central nervous system should enhance the drive for seeking food. The mechanism of the starvation-induced impairment in transport is unknown but cannot be caused by leptin itself because its levels decrease with fasting (21).
Lower in obesity, decreased after gastric surgery, does not cross blood brain barrier works by vagal stimulation, Moreover, high ghrelin increases ACTH, prolactin, and cortisol levels in humans (13, 230), which may explain the amenorrhea and behavioral changes observed in AN patients