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.
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
Role of GLP-1 in AT?
Fat – good or bad registrartraining2012
Fat – good or bad? Dr. Katarina Kos Senior Clinical Lecturer Obesity Lead, RD&E Exeter June 2012
Overview• What is the definition of obesity and fatness?• Fat tissue health• Regulation of appetite and adipose tissue mass: the brain-gut-fat axis
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
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 orBodpod)
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
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
Action of insulin on adipose tissue Increased FFA deposition with Insulin
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 anyBMI normal or ↓ normal to ↑ normal to ↑ normalGenes CGL1(AGPTAT2),CGLT FPLD2(LMNA), FPlD3 --- --- 2 (BSCL2) (PPARG) CAV1 Akt 2 ZIMPSE24Gluteal fat ↓↓↓ ↓↓ ↓ to ↑ 0-↓Limb fat ↓↓↓ ↓↓↓ ↓↓ 0-↓↓Trunk fat ↓↓↓ ↑↑↑ 0-↓↓ ↑↑-↓↓Hepatosteato present possible In generalized LD possiblesisDiabetes Very common Depending on In generalized LD Common mutationAcanthosis present present possible rarenigricansOther Hirsutism, bone cysts. CGLT2: --- Autoimmune disorders, low C3, --Features mental retardation, membranoproliferative cardiomyopathy glomerolunephritis
Good baby fat keeps adults slimAdults who retain their good baby fat may be buffered against obesity and type 2diabetes, 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 slimadults had more of it than fatter ones. Women appear to have more good brown fat
Adipose endocrinology Hypothalamu Tractus Feedback mechanisms s solitarius Leptin Adiponectin? Sympathetic innervationKos K, et al JCEM 2007
Leptin and blood brain barrier Banks W, AJP, 2002
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
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)
DPP-IV and fat tissue Why are DPP-IV inhibitors weight neutral? Kos K, Diabetes, Obesity and Metabolism, 2009
DPP-IV expression in abdominal Sc tissue 250 DPP IV mRNA expression in SU 200 150 * 100 50 0 Sc Sc Lean Obese
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’
When picking up his take away pizza: "You better cut the pizza in four pieces because Im not hungry enough to eat six.“Yogi Berra