Sexual dimorphism in the response of adipose mass and cellularity to graded caloric restriction.

OBJECTIVE: To investigate the effects of mild to moderate caloric restriction on parameters of body growth, fat mass, and adipose tissue cellularity in female and male Wistar rats. RESEARCH METHODS AND PROCEDURES: Three-month-old female and male Wistar rats were subjected to a chronic, mild to moderate caloric restriction paradigm (5%, 10%, or 20% reduction in caloric intake from ad libitum values) for 6 months. This was accomplished using a unique automated feeder system tailored to the food consumption levels of individual rats. Body weight and length, weight of lean organs, regional adipose mass, and adipose cellularity were measured before and after the diet restriction. RESULTS: Caloric restriction produced proportional decelerations in body weight increases in both genders, without significant changes in body length or lean organ mass. Marked and disproportional reductions in regional adipose tissue mass were produced at all levels of food restriction (even at 5% restriction). An unexpected finding was that in response to graded caloric restriction, female rats preserved adipose fat cell number at the expense of fat cell volume, whereas the converse was seen for male rats. DISCUSSION: These studies demonstrate a sexual dimorphism in the response to mild to moderate degrees of chronic caloric restriction. At low levels of caloric restriction, it is possible to affect regional adipose mass and cellularity while preserving lean organ mass.

Regional fat pad growth and cellularity in obese zucker rats: modulation by caloric restriction.

OBJECTIVE: To investigate, in young obese male Zucker rats, the effects of chronic food restriction and subsequent refeeding on: 1). parameters of nonadipose and adipose growth, 2). regional adipose depot cellularity [fat cell volume (FCV) and number], and 3). circulating leptin levels. RESEARCH METHODS AND PROCEDURES: Obese (fa/fa) and lean (Fa/?) male Zucker rats were studied from age 5 to 19 weeks. After baseline food intake monitoring, 10 obese rats were subjected to 58 days of marked caloric restriction from ad libitum levels [obese-restricted (OR)], followed by a return to ad libitum feeding for 22 days. Ten lean control rats and 10 obese control rats were fed ad libitum for the entire experiment. All rats were fed using a computer-driven automated feeding system designed to mimic natural eating patterns. RESULTS: After food restriction, OR rats weighed significantly less than did lean and obese rats and showed a significant diminution in body and adipose growth as compared with obese rats. Relative adiposity was not different between obese and OR rats and was significantly higher than that of lean rats. The limitation in growth of the adipose tissue mass in OR rats was due mostly to suppression of fat cell proliferation because the mean FCV in each of the four depots was not affected. Serum leptin levels of OR and obese rats were not different from each other but were significantly higher than those of lean rats. DISCUSSION: Marked caloric restriction affects obese male Zucker rats in a manner different from that of nongenetic rodent models (i.e., Wistar rats). In comparison with the response to caloric deprivation of Wistar rats, these calorically restricted obese male Zucker rats appeared to defend their relative adiposity and mean FCV at the expense of fat cell number. These findings indicate that genetic and/or tissue-specific controls override the general consequences of food restriction in this genetic model of obesity.

Dietary weight loss decreases serum angiotensin-converting enzyme activity in obese adults.

OBJECTIVE: To study the effect of dietary weight loss, postural change, and an oral glucose load on serum angiotensin-converting enzyme (ACE) activity in obese adults. RESEARCH METHODS AND PROCEDURES: Sixteen obese adult men and women with a mean body mass index of 35.7 +/- 4.3 kg/m(2) were studied after 1 week on a maintenance energy lead-in diet and after 5 weeks on an identical but 40% reduced-energy diet provided by the General Clinical Research Center (GCRC). ACE activity was measured spectrophotometrically. Plasma renin activity and serum aldosterone were measured by radioimmunoassay. RESULTS: All subjects lost weight, with a mean decrease in body weight of 7.0 +/- 2.1 kg or 6 +/- 3% of initial body weight (p < 0.00001). Systolic and diastolic blood pressure, supine plasma renin activity, and serum aldosterone levels decreased with weight loss (p < 0.05). Supine ACE activity decreased 23 +/- 12% with weight loss (p < 0.00001). Standing ACE activity, which was significantly higher than supine ACE activity before and after weight loss (p < 0.05), also decreased 18 +/- 17% with weight loss (p = 0.0007). A 75-g oral glucose load had no effect on serum ACE activity over a 3-hour period. DISCUSSION: In obese adults, serum ACE activity declines with modest weight loss, increases with postural change, and is unaffected by an oral glucose load.

Effects of TNF-alpha on glucose metabolism and lipolysis in adipose tissue and isolated fat-cell preparations.

We hypothesized that exposure to tumor necrosis factor-alpha (TNF-alpha) would significantly increase lactate production by adipose-tissue (AT) fragments and isolated adipocytes. We therefore examined the effects of TNF-alpha on the metabolism of epididymal AT explants during 24-hour tissue incubation. We also studied the effects of this 24-hour TNF-alpha tissue exposure on subsequent glucose metabolism and lipolysis by isolated adipocytes. Glycerol release into the medium was significantly increased (50%, P =.027) by exposure of the AT fragments to TNF-alpha (4 nmol/L) for 24 hours. During this time, glucose uptake from the medium and lactate release into the medium tended to increase, whereas leptin release into the medium tended to decrease, but these effects of TNF-alpha were not statistically significant. After the 24-hour AT-explant incubation, adipocytes were isolated by means of collagenase digestion from the AT fragments and subsequently tested in a short-term (60-minute) metabolic incubation. Prior exposure to TNF-alpha resulted in a significant increase in adipocyte glycerol release (P =.044), total glucose metabolism (P =.019), and lactate production (P =.037). With the exception of lactate, TNF-alpha produced no significant stimulation of the metabolites of glucose. The pattern of glucose metabolism elicited by TNF-alpha exposure differs from that usually attributed to a lipolytic hormone and suggests that the effects of TNF-alpha on glucose metabolism involve pathways separate from, or in addition to, its effects on lipolytic stimulation.