Skeletal muscle utilization of free fatty acids in women with visceral obesity.

Abstract

Visceral obesity is strongly associated with insulin resistance. One potential cause is increased availability of FFA. Alternatively, it has been proposed that there is impaired oxidation of lipid in individuals at risk for obesity. The extent to which either concept involves skeletal muscle is uncertain. To examine these opposing hypotheses, 17 healthy lean and obese premenopausal women, among whom cross-sectional area of visceral fat ranged from 18 to 180 cm2, participated in leg balance studies for measurement of FFA and glucose utilization during basal and insulin-stimulated conditions. A metabolic profile of skeletal muscle, based on enzyme activity, was determined in vastus lateralis muscle obtained by percutaneous biopsy. Visceral fat content was negatively correlated with insulin sensitivity (rates of leg glucose uptake and storage), but insulin resistance was not caused by glucose-FFA competition. During hyperinsulinemia, neither leg FFA uptake nor oxidation was increased in women with visceral obesity. During fasting conditions, however, rates of FFA uptake across the leg were negatively correlated with visceral adiposity as were activities of muscle carnitine palmitoyl transferase and citrate synthase. In summary, visceral adiposity is clearly associated with skeletal muscle insulin resistance but this is not due to glucose-FFA substrate competition. Instead, women with visceral obesity have reduced postabsorptive FFA utilization by muscle. (J. Clin. Invest. 1995Invest. . 95:1846Invest. -1853.) Key words: visceral obesity insulin resistance * human skeletal muscle * free fatty acid metabolism * carnitine palmitoyl transferase

Reduced whole-body lipid oxidation is associated with insulin resistance, but not with intramyocellular lipid content in offspring of type 2 diabetic patients

“…In parallel, impairment of muscle or plasma NEFA oxidation in obesity and type 2 diabetes have been reported by different groups [4][5][6]. The observation that in obese women [5] and type 2 diabetic patients [7] the impairment of fat oxidation was not reversed by considerable body weight reduction and that it was also detected in individuals with impaired glucose tolerance [8] would support the hypothesis of a primary genetic defect.…”

Could the low level of expression of the gene encoding skeletal muscle mitofusin-2 account for the metabolic inflexibility of obesity?

“…MFN2 protein expression in mitochondrial fractions from skeletal muscle of both Zucker rats and obese subjects was found to be significantly lower than in the lean counterparts [6]. This latter observation, coupled with the knowledge that muscle glucose oxidation during hyperinsulinaemia is impaired in obesity [7], might explain some of the metabolic alterations observed in the obese, insulin-resistant condition and might account for the loss of metabolic flexibility observed in obesity, explaining by what means it may be regained.…”

Brain neuropeptide Y and CCK and peripheral adipokine receptors: temporal response in obesity induced by palatable diet

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