Increase in visceral fat per se does not induce insulin resistance in the canine model.

OBJECTIVES: To determine whether a selective increase of visceral adipose tissue content will result in insulin resistance. METHODS: Sympathetic denervation of the omental fat was performed under general inhalant anesthesia by injecting 6-hydroxydopamine in the omental fat of lean mongrel dogs (n = 11). In the conscious animal, whole-body insulin sensitivity was assessed by the minimal model (SI ) and the euglycemic hyperinsulinemic clamp (SICLAMP ). Changes in abdominal fat were monitored by magnetic resonance. All assessments were determined before (Wk0) and 2 weeks (Wk2) after denervation. Data are medians (upper and lower interquartile). RESULTS: Denervation of omental fat resulted in increased percentage (and content) of visceral fat [Wk0: 10.2% (8.5-11.4); Wk2: 12.4% (10.4-13.6); P < 0.01]. Abdominal subcutaneous fat remained unchanged. However, no changes were found in SI [Wk0: 4.7 (mU/l)(-1) min(-1) (3.1-8.8); Wk2: 5.3 (mU/l)(-1) min(-1) (4.5-7.2); P = 0.59] or SICLAMP [Wk0: 42.0 × 10(-4) dl kg(-1) min(-1) (mU/l)(-1) (41.0-51.0); Wk2: 40.0 × 10(-4) dl kg(-1) min(-1) (mU/l) (-1) (34.0-52.0); P = 0.67]. CONCLUSIONS: Despite a selective increase in visceral adiposity in dogs, insulin sensitivity in vivo did not change, which argues against the concept that accumulation of visceral adipose tissue contributes to insulin resistance.

Inducible brown adipocytes in subcutaneous inguinal white fat: the role of continuous sympathetic stimulation.

Brown adipocytes (BA) generate heat in response to sympathetic activation and are the main site of nonshivering thermogenesis in mammals. Although most BA are located in classic brown adipose tissue depots, BA are also abundant in the inguinal white adipose tissue (iWAT) before weaning. The number of BA is correlated with the density of sympathetic innervation in iWAT; however, the role of continuous sympathetic tone in the establishment and maintenance of BA in WAT has not been investigated. BA marker expression in iWAT was abundant in weaning mice but was greatly reduced by 8 wk of age. Nonetheless, BA phenotype could be rapidly reinstated by acute ß3-adrenergic stimulation with CL-316,243 (CL). Genetic tagging of adipocytes with adiponectin-CreER(T2) demonstrated that CL reinstates uncoupling protein 1 (UCP1) expression in adipocytes that were present before weaning. Chronic surgical denervation dramatically reduced the ability of CL to induce the expression of UCP1 and other BA markers in the tissue as a whole, and this loss of responsiveness was prevented by concurrent treatment with CL. These results indicate that ongoing sympathetic activity is critical to preserve the ability of iWAT fat cells to express a BA phenotype upon adrenergic stimulation.

Cold-induced alteration of adipokine profile in humans.

Adipose tissue function and sympathetic nervous system (SNS) activity are tightly interconnected. Adipose tissue is densely innervated by the SNS. Adipokines secreted by adipose tissue are implicated in maintaining energy homeostasis, the control of blood pressure, immune system function, hemostasis, and atherosclerosis. Little is known about a direct effect of SNS activation on influencing adipose tissue endocrine function in humans. In 10 lean, healthy male volunteers, SNS was activated by whole-body exposure to cold for 2 hours; a group of 10 subjects served as controls. Vital parameters were evaluated, plasma adipokine levels were measured, and adipokine gene expression in subcutaneous abdominal adipose tissue was determined. Cold exposure caused an increase in cold sensation and a drop in body temperature and heart rate. Norepinephrine, but not epinephrine, plasma levels were elevated. Adiponectin plasma concentrations were acutely and significantly decreased. There was a trend of increased monocyte chemoattractant protein-1 plasma concentrations. Interleukin-6 and leptin levels increased and decreased, respectively, in both groups. Vascular endothelial growth factor plasma levels were unaffected. Subcutaneous adipokine gene expression was unchanged. Cold exposure caused SNS activation and differentially influenced adipokine secretion. Adiponectin levels were acutely reduced, whereas monocyte chemoattractant protein-1 concentrations tended to increase. No specific changes in leptin and IL-6 concentrations were detectable. The observed alterations appeared to be posttranscriptional because adipokine gene expression was found to be unaltered.