Methods for assessment, e.g., anthropometric indicators and imaging techniques, of several phenotypes of human obesity, with special reference to abdominal fat content, have been evaluated. The correlation of fat distribution with age, gender, total body fat, energy balance, adipose tissue lipoprotein lipase and lipolytic activity, adipose tissue receptors, and genetic characteristics are discussed. Several secreted or expressed factors in the adipocyte are evaluated in the context of fat tissue localization. The body fat distribution and the metabolic profile in nonobese and obese individuals is discussed relative to lipolysis, antilypolysis and lipogenesis, insulin sensitivity, and glucose, lipid, and protein metabolism. Finally, the endocrine regulation of abdominal visceral fat in comparison with the adipose tissue localized in other areas is presented.

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Subcutaneous and visceral adipose tissue : Their relation to the metabolic syndrome

Apres l'ingestion de glucose, l'insulino-secretion du pancreas est stimulee et la combinaison de l'hyperglycemie et de l'hyperinsulinemie doit induire la captation de glucose dans les territoires splanchique (foie et tube digestif) et peripherique (muscles) et la suppression de la production hepatique du glucose. Le but de cette conference est de prouver que, bien que la perturbation du metabolisme hepatique du glucose joue un role dans le maintien de l'etat diabetique, le foie ne joue probablement pas de role majeur dans le developpement precoce de l'hyperglycemie a jeun des DNID

Lilly lecture 1987. The triumvirate: beta-cell, muscle, liver. A collusion responsible for NIDDM.

Non-insulin-dependent diabetes mellitus (NIDDM) results from an imbalance between insulin sensitivity and insulin secretion. Both longitudinal and cross-sectional studies have demonstrated that the earliest detectable abnormality in NIDDM is an impairment in the body's ability to respond to insulin. Because the pancreas is able to appropriately augment its secretion of insulin to offset the insulin resistance, glucose tolerance remains normal. With time, however, the beta-cell fails to maintain its high rate of insulin secretion and the relative insulinopenia (i.e., relative to the degree of insulin resistance) leads to the development of impaired glucose tolerance and eventually overt diabetes mellitus. The cause of pancreatic "exhaustion" remains unknown but may be related to the effect of glucose toxicity in a genetically predisposed beta-cell. Information concerning the loss of first-phase insulin secretion, altered pulsatility of insulin release, and enhanced proinsulin-insulin secretory ratio is discussed as it pertains to altered beta-cell function in NIDDM. Insulin resistance in NIDDM involves both hepatic and peripheral, muscle, tissues. In the postabsorptive state hepatic glucose output is normal or increased, despite the presence of fasting hyperinsulinemia, whereas the efficiency of tissue glucose uptake is reduced. In response to both endogenously secreted or exogenously administered insulin, hepatic glucose production fails to suppress normally and muscle glucose uptake is diminished. The accelerated rate of hepatic glucose output is due entirely to augmented gluconeogenesis. In muscle many cellular defects in insulin action have been described including impaired insulin-receptor tyrosine kinase activity, diminished glucose transport, and reduced glycogen synthase and pyruvate dehydrogenase. The abnormalities account for disturbances in the two major intracellular pathways of glucose disposal, glycogen synthesis, and glucose oxidation. In the earliest stages of NIDDM, the major defect involves the inability of insulin to promote glucose uptake and storage as glycogen. Other potential mechanisms that have been put forward to explain the insulin resistance, include increased lipid oxidation, altered skeletal muscle capillary density/fiber type/blood flow, impaired insulin transport across the vascular endothelium, increased amylin, calcitonin gene-related peptide levels, and glucose toxicity.

Pathogenesis of NIDDM: A balanced overview

This review provides the reader with the up-to-date evidence-based basis for prescribing exercise as medicine in the treatment of 26 different diseases: psychiatric diseases (depression, anxiety, stress, schizophrenia); neurological diseases (dementia, Parkinson's disease, multiple sclerosis); metabolic diseases (obesity, hyperlipidemia, metabolic syndrome, polycystic ovarian syndrome, type 2 diabetes, type 1 diabetes); cardiovascular diseases (hypertension, coronary heart disease, heart failure, cerebral apoplexy, and claudication intermittent); pulmonary diseases (chronic obstructive pulmonary disease, asthma, cystic fibrosis); musculo-skeletal disorders (osteoarthritis, osteoporosis, back pain, rheumatoid arthritis); and cancer. The effect of exercise therapy on disease pathogenesis and symptoms are given and the possible mechanisms of action are discussed. We have interpreted the scientific literature and for each disease, we provide the reader with our best advice regarding the optimal type and dose for prescription of exercise.

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Exercise as medicine – evidence for prescribing exercise as therapy in 26 different chronic diseases

Excess intra-abdominal adipose tissue accumulation, often termed visceral obesity, is part of a phenotype including dysfunctional subcutaneous adipose tissue expansion and ectopic triglyceride storage closely related to clustering cardiometabolic risk factors. Hypertriglyceridemia; increased free fatty acid availability; adipose tissue release of proinflammatory cytokines; liver insulin resistance and inflammation; increased liver VLDL synthesis and secretion; reduced clearance of triglyceride-rich lipoproteins; presence of small, dense LDL particles; and reduced HDL cholesterol levels are among the many metabolic alterations closely related to this condition. Age, gender, genetics, and ethnicity are broad etiological factors contributing to variation in visceral adipose tissue accumulation. Specific mechanisms responsible for proportionally increased visceral fat storage when facing positive energy balance and weight gain may involve sex hormones, local cortisol production in abdominal adipose tissues, endocannabinoids, growth hormone, and dietary fructose. Physiological characteristics of abdominal adipose tissues such as adipocyte size and number, lipolytic responsiveness, lipid storage capacity, and inflammatory cytokine production are significant correlates and even possible determinants of the increased cardiometabolic risk associated with visceral obesity. Thiazolidinediones, estrogen replacement in postmenopausal women, and testosterone replacement in androgen-deficient men have been shown to favorably modulate body fat distribution and cardiometabolic risk to various degrees. However, some of these therapies must now be considered in the context of their serious side effects. Lifestyle interventions leading to weight loss generally induce preferential mobilization of visceral fat. In clinical practice, measuring waist circumference in addition to the body mass index could be helpful for the identification and management of a subgroup of overweight or obese patients at high cardiometabolic risk.

Pathophysiology of Human Visceral Obesity: An Update

The possible existence of regional differences in the antilipolytic action of insulin in human adipose tissue was investigated in vitro. Insulin-induced inhibition of glycerol release and insulin binding, measured in terms of receptor number, receptor affinity, and dissociation rates, were determined in omental and subcutaneous adipose tissue segments and isolated fat cells of 16 nonobese subjects who were undergoing elective abdominal surgery but were otherwise healthy. The sensitivity of the antilipolytic effect of insulin was higher in subcutaneous than in omental adipose tissue; the half-maximal effect was obtained with 1 and 3 μU/ml of insulin, respectively (P 125 I-insulin dissociated more rapidly from omental than from subcutaneous adipocytes in both the absence and the presence of excess native insulin. The data suggest that significant regional differences exist in the antilipolytic action of insulin in man; omental fat being less responsive than subcutaneous fat. The difference involves the insulin receptor affinity, which is caused at least partly by variations in the insulin dissociation rate but is also due to differences in insulin action at the postreceptor level.

Differences at the Receptor and Postreceptor Levels Between Human Omental and Subcutaneous Adipose Tissue in the Action of Insulin on Lipolysis

Omental fat cells were 30% smaller than those in subcutaneous regions. In omental fat cells with a mean diameter of 95 mu, the basal cAMP concentration was 50% lower, but the basal rate of glycerol release was three times as rapid as in subcutaneous (epigastric) fat cells of identical size. Added at maximal effective concentration, noradrenaline increased the level of cAMP and the rate of glycerol release more markedly in the omental than in the subcutaneous adipocytes, whereas the response to isopropyl noradrenaline was similar. Before starvation the lipolytic effects of noradrenaline and isopropyl noradrenaline, respectively, were identical in the two regions of subcutaneous adipose tissue investigated (femoral and hypogastric). The findings were well related to the tissue levels of cAMP induced by the two agents. During starvation noradrenaline and isopropyl noradrenaline increased the cAMP level and the rate of lipolysis in fat cells obtained from the hypogastric region, whereas noradrenaline decreased these parameters in femoral adipocytes. Starvation was associated with a more prominent inhibitory effect of phenylephrine on basal and isopropyl-noradrenaline-induced lipolysis in femoral than in hypogastric adipose tissue. In conclusion, differences exist between different regions of adipose tissue in their lipolytic responsiveness to noradrenaline, which seems related to the balance between alpha- and beta-adrenergic receptor response.

Regional differences in the control of lipolysis in human adipose tissue

The incidence of Type 1 diabetes has not increased but shifted to a younger age at diagnosis in the 0-34 years group in Sweden 1983 to 1998

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The incidence of Type I diabetes has not increased but shifted to a younger age at diagnosis in the 0-34 years group in Sweden 1983-1998.

The incidence of retinopathy 10 years after diagnosis in young adultpeople with diabetes: results from the nationwide population-basedDiabetes Incidence Study in Sweden (DISS).

https://care.diabetesjournals.org/content/diacare/26/2/349.full.pdf

The incidence of retinopathy 10 years after diagnosis in young adult people with diabetes : Results from the nationwide population-based Diabetes Incidence Study in Sweden (DISS)

The antilipolytic effect of insulin in vitro was investigated in conditions known to be associated with resistance to the effect of insulin on glucose metabolism. Human subcutaneous adipose tissue was obtained from 14 obese subjects before and during starvation for 7 days, 12 untreated non-insulin dependent diabetics (NIDDM), 6 untreated insulin dependent diabetics (IDDM), and 10 nonobese control subjects. The tissue was incubated with and without insulin in concentration ranging from 1-10,000 microunits/ml. Responsiveness (maximum effect) and sensitivity to insulin were determined under basal induction conditions, since insulin had a bimodal effect on noradrenaline stimulated lipolysis. Under normal conditions both insulin sensitivity and insulin responsiveness were positively correlated with the basal rate of lipolysis. In obesity, IDDM and NIDDM there were no change in insulin sensitivity or in insulin responsiveness. When the obese subjects were divided into one hyperinsulinemic group (6 individuals) and one group with normal fasting serum insulin levels (7 individuals) a similar antilipolytic effect of insulin was observed in the two groups. During starvation there was a 20-fold increase in insulin sensitivity (p less than 0.01) but no change in insulin responsiveness in femoral fat and only a decrease in responsiveness (p less than 0.01) in abdominal fat. The present data supports the view that antilipolysis in human fat cells is not involved in the insulin resistance seen in obesity, starvation, diabetes and hyperinsulinemia.

Jan Östman

Papers

Differences at the Receptor and Postreceptor Levels Between Human Omental and Subcutaneous Adipose Tissue in the Action of Insulin on Lipolysis

Regional differences in the control of lipolysis in human adipose tissue

The incidence of Type I diabetes has not increased but shifted to a younger age at diagnosis in the 0-34 years group in Sweden 1983-1998.

The incidence of retinopathy 10 years after diagnosis in young adult people with diabetes : Results from the nationwide population-based Diabetes Incidence Study in Sweden (DISS)

The antilipolytic effect of insulin in human adipose tissue in obesity, diabetes mellitus, hyperinsulinemia, and starvation☆