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

CONCENTRATIONS of certain hormone receptors are known to be reduced during ageing in several animal species1–4. Most relevant work, however, has been limited to intracellular hormone receptors such as those for steroids, and less is known about changes in cell surface receptors, including those for catecholamines. We have measured the concentration of β-adrenergic receptors in crude membrane fractions of mononuclear cells from human subjects of various ages. Receptor affinities for (—)3H-dihydroal-prenolol were esentially the same for all subjects. But a significant decrease in receptor concentration was observed in cells from older individuals.

Reduced beta-adrenergic receptor concentrations in ageing man.

The density but not the affinity of beta-adrenergic receptors declined significantly with age in rat pineal gland, corpus striatum, and cerebellum, as determined by the binding of tritiated dihydroalprenolol. Exposing rats to light for 12 hours increased the binding of this radioligand in 3-month-old but not in 24-month-old rats. The reduced responsiveness to catecholamines seen in aging may be due to a decrease in the number of beta-adrenergic receptors which, in turn, may be caused by an impaired capacity of receptors in aged animals to adapt to changes in adrenergic neuronal input.

beta-Adrenergic receptors in aged rat brain: reduced number and capacity of pineal gland to develop supersensitivity.

To estimate the regional subcutaneous glycerol production rate in normal and obese humans, the venous arterialized plasma glycerol, interstitial glycerol in the subcutaneous adipose tissue together with adipose tissue blood flow (ATBF, ml/100 g.min) were measured in the postabsorptive state and for 2 h after ingestion of 100 g of oral glucose. Eight lean and eight obese men with normal oral glucose tolerance tests were investigated with the subcutaneous microdialysis technique and 133Xe clearance. In the postabsorptive state, the interstitial glycerol concentrations in lean and obese subjects were 170 +/- 21 vs. 282 +/- 28 microM (P less than 0.01) and 156 +/- 23 vs. 225 +/- 12 microM (P less than 0.05) in the abdominal and femoral subcutaneous adipose tissue, respectively. The corresponding arterial glycerol levels were 54 +/- 4 vs. 75 +/- 14 microM (NS). Abdominal ATBF was greater in lean subjects (3.2 +/- 0.6 vs. 1.6 +/- 0.3; P less than 0.05), whereas femoral ATBF was similar in both groups (2.7 +/- 0.4 vs. 2.4 +/- 0.7). Estimated mean local glycerol release (mumol/100 g.min) was similar in the lean and obese group (0.16 +/- 0.03 vs. 0.20 +/- 0.05 and 0.18 +/- 0.02 vs. 0.17 +/- 0.04) in the abdominal and femoral site, respectively. We conclude that glycerol production from the subcutaneous tissue is increased in obesity, irrespective of adipose tissue distribution. This enhancement is due to the increased adipose tissue mass.

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Glycerol production in subcutaneous adipose tissue in lean and obese humans.

Control of lipolysis and its relevance to development of obesity in man

Lipolysis (release of glycerol and free fatty acids) of subcutaneous human adipose tissuein vitro has been investigated in relation to relative body weight and fat cell size. Studying 86 persons, there was a highly significant logarithmic relation between relative body weight, fat cell size and lipid content of subcutaneous adipose tissue obtained from the abdominal region. Even in extreme obesity a mean fat cell diameter of 135 μ was generally not exceeded. In these cases overweight is due to hypertrophy as well as hyperplasia of adipose tissue. — The basal FFA and glycerol release, calculated on the basis of the lipid content, did not significantly differ in normal and overweight persons. The lipolysis of the individual cell increased, however, with increasing cell diameter. The quotient of resterification (FFA release: glycerol release) was significantly lower in obesity. — When lipolysis was stimulated with norepinephrine, theophylline or dibutyryl-cyclic AMP, the dose response relations were similar in obesity and normal weight. — The stimulation of lipolysis, expressed as % of baseline, was diminished in obesity. Stimulation with dibutyryl-cyclic-AMP was negatively correlated to the cell diameter. — The absolute release of metabolites per fat cell after stimulation with norepinephrine, theophylline or dibutyryl-cyclic AMP was positively correlated with the fat cell diameter. — Addition of glucose resulted in an increment in glycerol release and an inhibition of FFA release. However, the correlation of lipolysis with fat cell diameter was not affected. — The observations suggest that large fat cells are provided with additional total lipase. Under basal conditions the relation of inactive pro lipase to active lipase seemed to change in favour of the active enzyme.

/pdf/effects-of-norepinephrine-theophylline-and-dibutyryl-cyclic-9c03p6t976.pdf

Effects of norepinephrine, theophylline and dibutyryl cyclic AMP on in vitro lipolysis of human adipose tissue in obesity.

On isolated human adipose tissue of 80 lean und 50 obese subjects of 18 to 72 years of age the mean fat cell diameter and the in vitro release of glycerol and free fatty acids were

C. Hesse-Wortmann

Papers

Effects of norepinephrine, theophylline and dibutyryl cyclic AMP on in vitro lipolysis of human adipose tissue in obesity.

Altersabhängigkeit der Fettzellgrösse und der lipolytischen Aktivität im menschlichen Fettgewebe

Age dependence of fat cell size and lipolytic activity in human adipose tissue