The regional distribution of body fat has repeatedly been found to be a significant and independent risk factor for cardiovascular disease in both obese men and women. To determine whether abnormalities in the lipid-lipoprotein profile and systolic and diastolic blood pressure are related to specific fat depots early in the course of obesity, we used magnetic resonance imaging to measure accurately intraabdominal and subcutaneous fat masses in 14 obese [body mass index (BMI; in kg/m2) 30 +/- 1.3] and 10 nonobese (BMI: 21 +/- 0.5) adolescent girls matched for age and Tanner stage of development. Intraabdominal and subcutaneous fat depots were two- to threefold greater in obese than in nonobese girls (P < 0.01). Total cholesterol, triacylglycerol, low-density-lipoprotein (LDL) cholesterol, basal insulin, and systolic and diastolic blood pressure were significantly higher in obese adolescent girls than in control subjects. In obese girls, intraabdominal fat but not BMI or waist-to-hip ratio was highly correlated with basal insulin (r = 0.55, P < 0.04), triacylglycerols (r = 0.53, P < 0.03), and high-density-lipoprotein (HDL) cholesterol (r = -0.54, P < 0.04). Femoral adipose tissue was inversely related to triacylglycerol (r = -0.51) and LDL cholesterol (r = -0.56, P < 0.05) concentrations in obese girls. The study indicates that early in the natural history of obese adolescent girls, cardiovascular risk factors are related to the amount of intraabdominal fat.

To establish whether alterations in insulin action and secretion and their relationship to body fat distribution occur early in the course of developing obesity, we studied 14 obese adolescent girls [13.2 +/- 0.7 yr, body mass index (BMI) 32 +/- 1.4], 16 nonobese young women (24.0 +/- 0.6 yr, BMI 21.0 +/- 0.9). Insulin action was assessed by a sequential two-step (8 and 40 mU,m-2.min-1) euglycemic insulin clamp in combination with [1-13C]glucose and indirect calorimetry. Insulin secretion was determined by the hyperglycemic clamp technique (6.9 mmol/l). Magnetic resonance imaging was used to quantify visceral and subcutaneous abdominal fat depots. In obese girls, an impairment in glucose disposal was present with both insulin doses; at the higher dose, rates of glucose uptake were reduced by 30% in nonobese girls (240 +/- 30 vs. 340 +/- 19 mg.m-2.min-1, P < 0.05) and by an additional 29% (170 +/- 17 mg.m-2.min-1, P < 0.05) in obese girls. Insulin infusion failed to stimulate glucose oxidation and to suppress lipid oxidation only in obese girls. Suppression of free fatty acid levels, but not hepatic glucose production, was decreased in obese girls compared with controls. Fasting and glucose-stimulated insulin responses were greater in obese than in nonobese adolescents, who, in turn, had greater responses than lean women. In obese girls, visceral fat, but neither waist-to-hip circumference ratio nor subcutaneous fat, was highly correlated with basal insulin secretion (r = 0.89, P < 0.001), stimulated insulin secretion (r = 0.61, P < 0.05), and insulin resistance (r = -0.87, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Leptin, the OB gene product, is an adipocyte-derived circulating protein. In several rodent models of obesity, such as the db/db mice, fa/fa rats, and ventromedial hypothalamus-lesioned mice, as well as adult obese subjects, leptin mRNA expression and the circulating levels are elevated, suggesting resistance to its action. However, it is unknown whether the rise in leptin concentration occurs early in the natural evolution of human obesity or is a chronic adaptation to the obese state. Moreover, whether the distribution of body fat (i.e., visceral vs. subcutaneous abdominal fat) influences circulating leptin levels has not been assessed. We have determined in a group of obese and nonobese children and young adults whether leptin levels 1) are increased early in the development of obesity, 2) are related to a specific fat depot measured by magnetic resonance imaging, 3) vary during hyperinsulinemic, euglycemic, and hyperglycemic clamp studies, and 4) are different in males vs. females. In the basal state, leptin levels were elevated in obese children. Children and adults demonstrated a strong positive correlation between leptin concentrations and the subcutaneous fat depot (r = 0.84, P < 0.001). Surprisingly, a weaker correlation was found with visceral fat mass (r = 0.59, P = 0.001). Leptin levels remained unchanged under both euglycemic and hyperglycemic hyperinsulinemic conditions in both obese and nonobese subjects. A pronounced effect of gender on leptin levels was also observed. We conclude that, early in the development of juvenile obesity, leptin concentrations are elevated and are more closely linked to subcutaneous than visceral fat mass. Acute increases in insulin concentrations do not affect circulating leptin levels.

We hypothesized that cardiac and respiratory modulation of postganglionic peroneal activity appeared in an age-related manner. In anesthetized, paralyzed and artificially ventilated piglets, simultaneous recordings of efferent phrenic and peroneal discharges were obtained during hyperoxia (fraction of inspired oxygen, FiO2 = 1.0) and hypoxia (FiO2 = 0.1). Spectral analyses of peroneal and aortic blood pressure signals revealed peaks at the cardiac frequency (3.25-5.0 Hz). Coherence analysis showed that these two signals were highly correlated at those frequencies, providing evidence for baroreceptor entrainment. Statistically significant (p < 0.05) increases of coherence values were observed during hypoxic stimulation. Such results were observed in most animals despite age, and provided evidence of a potent mechanism for insuring vasomotor tone even in newborn animals. In contrast, spontaneous respiration-related peroneal discharges were observed only in animals > or = 20 d old. In animals < 20 d old, hypoxic stimulation elicited respiration-related discharges in peroneal activity. In many cases, peroneal hypoxic discharges exhibited an immature biphasic response pattern despite the presence of a mature response pattern of phrenic activity. Such findings suggest a developmental lag in the linkages of respiratory and sympathetic controlling networks.

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