Lipolytic activity. Acute experimental increases in plasma free fatty acid (FFA) concentration, induced by infusion of a lipid emulsion, impair insulin-mediated suppression of hepatic glucose production and insulin-mediated stimulation of glucose disposal in a dose-dependent manner (159, 160). However, the influence of endogenous adipose tissue lipolytic activity and plasma FFA concentration on insulin sensitivity in people with obesity is not clear because of conflicting results from different studies. Specifically, the basal rates of FFA release into the systemic circulation and plasma FFA concentration have been reported as either greater (21, 161, 162) or not different (101, 163, 164) in people who are overweight/obese and insulin resistant compared with those who are insulin sensitive. The importance of circulating FFA as a cause of insulin resistance in MUO is further questioned by studies that found no difference in basal, postprandial, and 24-hour plasma FFA concentrations in people with obesity compared with those who are lean and more insulin sensitive (122, 165). The reason(s) for the differences between studies are not clear, but could be related to the considerable individual day-to-day variability in FFA kinetics and plasma FFA concentration and differences in compensatory hyperinsulinemia and insulin-mediated suppression of adipose tissue lipolytic rate in people with insulin resistance (122, 165, 166). Differences in the percentage of women between study cohorts will also affect the comparison of FFA kinetics and concentrations between MHO and MUO groups, because the rate of the appearance of FFA in the bloodstream in relationship to fat-free mass or resting energy expenditure is greater in women than in men (167, 168), yet muscle (169) and liver (170, 171) insulin sensitivity are greater in women. Taken together, these studies suggest that differences in subcutaneous adipose tissue lipolytic activity do not explain the differences in insulin sensitivity between people with MHO and MUO. However, it is still possible that differences in lipolysis of IAAT and portal vein FFA concentration (172) or differences in the effect of FFA on tissue (muscle or liver) insulin action contribute to the differences in insulin resistance between the two groups.
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