Search

Upper body obese (UBO) subjects have greater cardiovascular disease risk than lower body obese (LBO) or lean subjects. Obesity is also associated with hypertriglyceridemia that may involve greater production and impaired removal of very-low-density lipoprotein (VLDL)-triglycerides (TG). In these studies, we assessed the impact of body composition on basal VLDL-TG production, VLDL-TG oxidation, and VLDL-TG storage. VLDL-TG kinetics were assessed in 10 UBO, 10 LBO, and 10 lean women using a bolus injection of [1-[sup.14]C]VLDL-TG. VLDL-TG oxidation was measured by [sup.14]C[O.sub.2] production (hyamine trapping) and VLDL-TG adipose tissue storage by fat biopsies. Insulin sensititvity was assessed by the hyperinsulinemic-euglycemic clamp technique and body composition by dual X-ray absorptiometry in combination with computed tomography. Hepatic VLDL-TG production was significantly greater in UBO than in lean women [([micro]mol/min) UBO: 64.8 (SD 40.0) vs. LBO: 42.5 (SD 25.6) vs. lean: 31.8 (SD 13.3), P = 0.04], whereas VLDL-TG oxidation was similar in the three groups and averaged 20% of resting energy expenditure [([micro]mol/min) UBO: 38.3 (SD 26.5) vs. LBO: 23.5 (SD 13.5) vs. lean: 21.1 (SD 9.7), P = 0.09]. In UBO women, more VLDL-TG was deposited in upper body subcutaneous fat [VLDL-TG redeposition in abdominal adipose tissue ([micro]mol/min): UBO: 5.0 (SD 2.9) vs. LBO: 4.0 (SD 3.2) vs. lean: 1.3 (SD 1.0), ANOVA P = 0.01]; in LBO women, more VLDL-TG was deposited in femoral fat [VLDL-TG redeposition in femoral adipose tissue ([micro]mol/min): UBO: 5.1 (SD 3.1) vs. LBO: 5.8 (SD 4.3) vs. lean: 2.3 (SD 1.5), ANOVA P = 0.04]. Only a small proportion of VLDL-TG (8-16%) was partitioned into redeposition in either group. We found that elevated VLDL-TG production without concomitant increased clearance via oxidation and adipose tissue redeposition contributes to hypertriglyceridemia in UBO women. very-low-density lipoprotein-triglycerides; body composition; obesity; tracers; fat biopsies

The ability of growth hormone (GH) to stimulate lipolysis and cause insulin resistance in skeletal muscle may be causally linked, but the mechanisms remain obscure. We investigated the impact of GH on the turnover of FFA and VLDL-TG, intramuscular triglyceride content (IMTG), and insulin sensitivity (euglycemic clamp) in nine healthy men in a randomized double-blind placebo-controlled crossover study after 8 days treatment with (A) Placebo + Placebo, (B) GH (2 mg daily) + Placebo, and (C) GH (2 mg daily) + Acipimox (250 mg X 3 daily). In the basal state, GH (B) increased FFA levels (P < 0.05), palmitate turnover (P < 0.05), and lipid oxidation (P = 0.05), but VLDL-TG kinetics were unaffected. Administration of acipimox (C) suppressed basal lipolysis but did not influence VLDL-TG kinetics. In the basal state, IMTG content increased after GH (B; P = 0.03). Insulin resistance was induced by GH irrespective of concomitant acipimox (P < 0.001). The turnover of FFA and VLDL-TG was suppressed by hyperinsulinemia during placebo and GH, whereas coadministration of acipimox induced a rebound increase FFA turnover and VLDL-TG clearance. We conclude that these results show that GH-induced insulin resistance is associated with increased IMTG and unaltered VLDL-TG kinetics; we hypothesize that fat oxidation in muscle tissue is an important primary effect of GH and that circulating FFA rather than VLDL-TG constitute the major source for this process; and the role of IMTG in the development of GH-induced insulin resistance merits future research. acipimox; lipolysis; very-low-density lipoprotein-triglyceride kinetics; hyperinsulinemic euglycemic clamp; insulin sensitivity

It is unknown whether short-term modulation of substrate supply affects cardiac performance in heart failure patients with chronic ischemic myocardium. The aim of this study was to determine whether modulation of myocardial substrate metabolism with insulin and free fatty acids (FFAs) affects contractile function of chronically stunned (CST) and hibernating (HIB) myocardium at rest and after maximal exercise. We studied eight nondiabetic patients with ejection fraction (EF) 30 [+ or -] 4% (SE) and CST/ HIB in 49 [+ or -] 6% of the left ventricle: 36 [+ or -] 6% CST and 13 [+ or -] 2% HIB as determined by [sup.99m]Technetium-Sestamibi single photon emission computed tomography (SPECT) and [sup.18]F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Each patient was subjected to a 3-h infusion of 1) saline, 2) insulin-glucose (i.e., euglycemic insulin clamp; high insulin, suppressed FFA), and 3) somatostatin-heparin (suppressed insulin, high FFA). Echocardiographic endpoints were global EF and regional contractile function [maximum velocity ([V.sub.max]) and strain rate ([[epsilon].sub.max])] as determined by tissue Doppler imaging at steady state and after maximal exercise. EF was similar at baseline and steady state and increased after exercise to 36 [+ or -] 5% (P < 0.05). Baseline regional [V.sub.max] and [[epsilon].sub.max] were highest in control, intermediate in CST and HIB, and lowest in infarct regions (P < 0.05). Steadystate EF, [V.sub.max], and [[epsilon].sub.max] were not affected by metabolic modulation in any region. After maximal exercise, contractile function increased in control, CST, and HIB (P < 0.05), but not in infarct, regions. Exercise-induced contractile increments were unaffected by metabolic modulation. Metabolic modulation does not influence contractile function in CST and HIB regions. Chronic ischemic myocardium has preserved ability to adapt to extreme, short-term changes in substrate supply at rest and after maximal exercise. glucose; hibernation; myocardial stunning

The relationship between episodic growth hormone (GH) secretion and muscle entropy, body composition and physical fitness was analyzed in normal human volunteers via a deconvolution technique. Analysis of lean and fat tissue distribution via computerized tomography and dual-energy X-ray absorption scan indicated the presence of reduced levels of GH secretion in older humans compared to younger volunteers. Furthermore, abdominal fat mass acted as a negative determinant of the amount and pattern of GH release in the fed state.

The role of the renin-angiotensin-aldosterone system (RAAS) in growth hormone (GH)-induced fluid and sodium retention was analyzed in healthy human subjects. Administration of GH and concomittant blockade of the RAAS in healthy human subjects induced significant elevations in extracellular volume and significant reductions on bioimpedance. On the other hand, concomittant administration of GH and an aldosterone antagonist did not alter bioimpedance or extracellular volume.

The role of insulin-like growth factor-I (IGF-I) in the regulation of pulsatile insulin release was analyzed in eight healthy humans. Deconvolution analysis of insulin concentration time series during modest hyperglycemia and supraphysiological IGF-I infusions in healthy adults indicated the inhibitory effects of IGF-I on pulsatile insulin secretion. However, glucose concentration remained constant during IGF-I infusions due to increased insulin sensitivity and direct tissue effects of IGF-I.

Insulin-like growth factor I (IGF-I) increases the body's sensitivity to insulin. It induces glucose metabolism and the production of free fatty acids and ketone bodies. The effects of IGF-I were studied by monitoring changes in free fatty acid and ketone body levels in the forearm muscles of human subjects. Their whole body glucose levels were also recorded. The hypoglycemic condition induced by IGF-I could not be effectively countered by growth hormone and glucagon.