Search

Weight loss (WL) by hypocaloric diet decreases adipocyte lipolysis and fat oxidation, adaptations that might predispose individuals to regain weight. Our hypothesis was that the addition of endurance exercise (EX) to dietary-induced WL (6 mo; 250-350 kcal/day deficit) would prevent declines in abdominal (ABD) and gluteal (GLT) adipocyte lipolysis and fat oxidation in obese older women. At baseline, the WL (n = 9) and WL+EX (n = 11) groups had similar body composition, fat distribution, aerobic fitness (VO2max), and resting fat metabolism. Reductions in body weight (WL = 11%, WL+EX = 8%), percent body fat, and intra-abdominal fat area with the interventions were similar in both groups, but VO2max increased (9%, P < 0.01) only in the WL+EX group. Basal and adrenergic receptor- and postreceptor-stimulated lipolysis in ABD and GLT adipocytes decreased (20-70%, P < 0.05) in the WL group but did not change in the WL+EX group. Fat oxidation decreased (38%, P < 0.05) in the WL group but not in the WL+EX group. The changes in fat oxidation and GLT lipolysis differed significantly between groups. Fat oxidation correlated positively with ABD and GLT adipocyte basal lipolysis at baseline (r = 0.45 and r = 0.53, P < 0.05), and the changes in fat oxidation with the interventions correlated positively with changes in ABD and GLT adipocyte basal lipolysis (r = 0.50 and r = 0.42. P < 0.05) in the entire group of women. These results indicate that exercise counteracts the decline in fat oxidation with WL, in part by maintaining adipocyte lipolytic responsiveness in some weight-reduced postmenopausal women.

This study determines whether there are regional differences in lipolysis and whether adipocyte lipolysis is associated with the degree of visceral adiposity and its metabolic complications in 32 obese (28-37 kg/m2), nondiabetic, postmenopausal women. In vitro lipolysis was measured in the basal state and after addition of epinephrine (Epi), Epi plus yohimbine, Epi plus propranolol, and N6,2'-O-dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) in abdominal (ABD) and gluteal (GLT) adipocytes. Upper body obese [UBO, waist-to-hip ratio (WHR) > or = 0.80, n = 19] women had a greater intra-abdominal fat area (IA, 199 +/- 50 vs. 142 +/- 28 cm2) and Epi-stimulated lipolysis (ABD: 1.60 +/- 1.10 vs. 0.95 +/- 0.54 mumol glycerol.10(6) cells-1.2h; GLT: 1.14 +/- 0.70 vs. 0.66 +/- 0.42 mumol glycerol.10(6) cells-1.2 h) than lower body obese (LBO, WHR < 0.80, n = 13) women. The UBO women also had lower high-density lipoprotein cholesterol (1.39 +/- 0.40 vs. 1.64 +/- 0.39 mmol/l, P < 0.05), higher plasma triglycerides (1.89 +/- 0.48 vs. 1.44 +/- 0.56 mmol/l, P < 0.05), and higher fasting insulin levels (154 +/- 57 vs. 118 +/- 33 pmol/l, P < 0.05) than LBO women. Basal, adrenergic receptor-mediated, and DBcAMP-stimulated lipolytic rates in ABD and GLT adipocytes were positively correlated with IA (r = 0.44-0.76, P < 0.05, n = 28). In both UBO and LBO women, Epi-stimulated lipolysis was higher (+30%, P < 0.05) in ABD than GLT adipocytes. These results show that, in postmenopausal women, visceral obesity is associated with increased rates of lipolysis in both ABD and GLT subcutaneous adipocytes. The findings also indicate that Epi-stimulated lipolysis is greater in ABD than GLT adipocytes regardless of fat distribution.

The effect of long-term aerobic exercise training on insulin action was determined in older individuals by comparing insulin sensitivity and maximal responsiveness in 11 master athletes [63.5 +/- 1.9 (SE) yr] and 10 age- and body fat-matched sedentary individuals. Maximal aerobic power was higher and the waist-to-hip ratio (WHR) was lower in the athletes, but there were no differences in body weight, percent body fat, or fat-free mass between groups. Fasting plasma glucose levels and glucose and insulin responses during oral glucose tolerance tests were lower in the athletes. The insulin concentration producing a half-maximal increase in glucose disposal (EC50) during a three-step hyperinsulinemic-euglycemic glucose clamp was 41% lower in the athletes than in controls (483 +/- 30 vs. 822 +/- 132 pmol/l, P < 0.05), whereas maximal responsiveness was comparable (81.0 +/- 4.4 vs. 85.5 +/- 8.3 mumol.kg fat-free mass-1.min-1, P = not significant). The EC50 correlated with maximal aerobic power (r = -0.62, P < 0.01) and WHR (r = 0.52, P < 0.05), but in multiple regression analyses WHR was the only variable independently related to EC50. These results indicate that long-term aerobic exercise training is associated with enhanced insulin sensitivity and a lower WHR in older individuals. This finding suggests that regular aerobic exercise may prevent the age-associated increase in abdominal obesity and insulin resistance.

Insulin hyperpolarizes. This raises the questions: is hyperpolarization a means by which insulin exerts some of its other effects, and can electrically induced hyperpolarization mimic insulin action on membrane functions? A technique was devised to study the latter question. The technique permits electrical hyperpolarization of a segment of whole muscle. Rat caudofemoralis muscle was threaded into a triple sucrose-gap chamber. Continuous flow of sucrose displaced interstitial fluid of muscle segments in the gaps. In one electrolyte compartment between gaps was placed an anode and in the other a cathode. The muscle segment in the anodal compartment was hyperpolarized continuously for 30 min, probably by about 1.5 mV. Uptake of deoxyglucose was increased in the hyperpolarized muscle segment. This increase, by 39%, was highly significant. It was probably smaller than the twofold increase elicited by insulin (100 mU/ml), but not than the possible effect produced by 10 mU/ml. The effect of hyperpolarization was specific for the D-glucose transport system because uptake of L-glucose was not altered.

These experiments were designed to test the hypothesis that insulin-induced hyperpolarization is a link in the chain of events leading to stimulation of glucose transport. External potassium concentration, [K+]o, was increased by equimolar substitution of KCl for NaCl, a method known to cause cell swelling, and by substitution of [K+]o for [Na+]o with maintenance of constant [K+]o X [Cl-]o product, a method that does not cause cell swelling. When there was constant KCl product, even at 76.8 meq [K+]o insulin continued to hyperpolarize, although by only approximately 44% as much as in normal [K+]o, and insulin-stimulated 2-deoxyglucose uptake was only approximately 60% of that at normal [K+]o. With equimolar substitution of KCl for NaCl: electrical potential difference across cell membranes of surface fibers of rat caudofemoralis muscle decreased with logarithm [K+]o, in the presence or absence of insulin. Insulin-induced hyperpolarization decreased as [K+]o increased and disappeared at 36 mM [K+]o. The amount of insulin bound to its receptors in 1 h was not affected by [K+]o over the range studied. Insulin effects on membrane potential and on 2-deoxyglucose uptake, as both were altered by [K+]o, correlated well. As the probe moved in depth through the first six fibers there was stepwise decrease in depolarization in high [K+]o in the absence of insulin. Insulin hyperpolarized the deepest of these fibers, even when it did not hyperpolarize the outermost. The decrease in insulin-induced hyperpolarization as [K+]o increases is consistent with the hypothesis that insulin hyperpolarizes by decreasing the ratio PNa/PK.

Antibodies to insulin receptors have been reported to have some insulinlike metabolic effects. If insulin-induced electrical hyperpolarization of skeletal muscle is part of the transduction chain between receptor and certain metabolic responses, then receptor antiserum should hyperpolarize. The Jacobs antiserum (rabbit antiserum against rat liver insulin receptor) hyperpolarized rat caudofemoralis muscle. Maximum effect, about 4.5 mV, occurred at 1:10,000 dilution, half maximum at about 1:40,000. Maximum effect of antiserum was only as great as half maximum hyperpolarization by insulin on this muscle. 2-Deoxyglucose uptake was also stimulated by antiserum but required greater concentration than for hyperpolarization, and the stimulation was only by about one-third the maximum effect of insulin.