Insulin sensitivity during acute elevation of NEFA: influence of fat composition and gender

Abstract

Conditions associated with impairments in insulin sensitivity (SI), such as obesity and type-II diabetes (T2D), often present with elevated NEFA. While lipid infusion studies have shown that increasing NEFA can impair glucose metabolism (1) , there are relatively few studies investigating the effect of NEFA elevation following fat loads of differing composition.Sixty healthy volunteers participated in a single-blind crossover trial. Subjects were randomly assigned to either 0.75 g/kg bodyweight (bw) of palm stearin (SFA) or 0.65 g/kg bw of palm stearin and 0.1 g/kg bw of DHA-rich fish oil (n-3 PUFA) on separate occasions; study visits for females were conducted at 4-week intervals to control for the menstrual cycle. The oils were emulsified into chocolate drinks and given as a bolus at baseline (0 min), followed by smaller drinks every 30 min. At 60 min, an infusion of heparin (500 IU bolus + 0.4 IU/ kg bw/min) was administered to activate lipoprotein lipase (2) . At 240 min, a hyperinsulinaemic (HI)-euglycaemic clamp (1 mU/kg/min) was initiated. SI was calculated as the mean glucose infusion rate for the last 30 min of the 150 min clamp, either adjusted for bw or fat-free mass (ffm). Plasma NEFA increased with the heparin infusion and subsequently declined during the HI clamp (Fig. 1); NEFA did not differ between the two study days. Insulin sensitivity was significantly greater during the consumption of n-3 PUFA than SFA for males but not females (Table).Our data suggest that the substitution of a relatively small amount of SFA for n-3 PUFA during oral fat feeding with heparin infusion acutely increases SI in males. The reasons for the gender-specific effect are unclear, but there is some evidence to indicate that men may be more sensitive to the effects of lipid-induced impairments in SI (3,4) . Long-term trials are needed to investigate whether these acute study results could infer any benefit of dietary fish oil supplementation in improving SI in males.