Regulation of free fatty acid metabolism by insulin in humans: Role of lipolysis and reesterification

Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2230.
The American journal of physiology (Impact Factor: 3.28). 12/1992; 263(6 Pt 1):E1063-9.
Source: PubMed


The regulation of lipolysis, free fatty acid appearance into plasma (FFA R(a)), an FFA reesterification and oxidation were examined in seven healthy humans infused intravenously with insulin at rates of 4, 8, 25, and 400 mU.m-2.min-1. Glycerol and FFA R(a) were determined by isotope dilution methods, and FFA oxidation was calculated by indirect calorimetry or by measurement of expired 14CO2 from infused [1-14C]palmitate. These measurements were used to calculate total FFA reesterification, primary FFA reesterification occurring within the adipocyte, and secondary reesterification of circulating FFA molecules. Lipolysis, FFA R(a), and secondary FFA reesterification were exquisitely insulin sensitive [the insulin concentrations that produced half-maximal suppression (EC50), 106 +/- 26, 91 +/- 20 vs. 80 +/- 16 pM, P = not significant] in contrast to insulin suppression of FFA oxidation (EC50, 324 +/- 60, all P < 0.01). The absolute rate of primary FFA reesterification was not affected by the increase in insulin concentration, but the proportion of FFA molecules undergoing primary reesterification doubled over the physiological portion of the insulin dose-response curve (from 0.23 +/- 0.06 to 0.44 +/- 0.07, P < 0.05). This served to magnify insulin suppression of FFA R(a) twofold. In conclusion, insulin regulates FFA R(a) by inhibition of lipolysis while maintaining a constant rate of primary FFA reesterification.

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    • "Onset of type 2 diabetes is commonly preceded by early metabolic changes (prediabetes), including a progressive development of insulin resistance, which is first compensated by the overproduction of insulin by beta cells until the insulin production becomes inadequate (Hsueh et al., 2010). The effects of insulin include a reduction in blood glucose and free fatty acids, the latter being derived from a suppression of lipolysis (Campbell et al., 1992). Hence, assuming equal insulin levels, higher blood glucose levels are related to lower insulin sensitivity. "
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    ABSTRACT: The aim of the present study was to assess the relationship between serum concentrations of several persistent organic pollutants and insulin resistance markers in a cohort of women with a history of gestational diabetes mellitus. ∑POPs was computed as the sum of individual serum POP concentrations. No statistically significant associations were found between levels of any POP and fasting glucose. However, polychlorinated biphenyl (PCB) congeners 138 and 180 were positively associated with 2-h glucose levels and PCB 180 also with fasting immunoreactive insulin (IRI). We also found a positive association of p,p'- dichlorodiphenyldichloroethylene (p,p'- DDE), PCBs (138, 153, and 180), hexachlorobenzene, and ∑POPs with 2-h IRI. Serum concentrations of PCBs (138, 153, and 180), hexachlorobenzene, and ∑POPs were also positively associated with homeostasis model assessment (HOMA2-IR) levels. Moreover, p,p'- DDE, PCBs (138, 153 and 180), hexachlorobenzene, and ∑POPs were negatively associated with Insulin Sensitivity Index (ISI-gly) levels. No significant association was found between glycated hemoglobin and the concentrations of any POP. The removal of women under blood glucose lowering treatment from the models strengthened most of the associations previously found for the whole population. Our findings suggest that exposure to certain POPs is a modifiable risk factor contributing to insulin resistance. Copyright © 2014 Elsevier Inc. All rights reserved.
    Environmental Research 11/2014; 136C:435-440. DOI:10.1016/j.envres.2014.11.007 · 4.37 Impact Factor
    • "The shift of CHO to fat oxidation during exercise might be explained by the reduced hyperglycemia and hyperinsulinemia during the postprandial period following LGI snack bar consumption (Sun et al., 2012b). The increased muscle glycogen synthesis and CHO availability (Wee et al., 2005), together with the suppressed lipolysis and fat availability (Campbell et al., 1992; Wu et al., 2003), might be attributed to the increased CHO oxidation and decreased fat oxidation during exercise following the HGI snack bar consumption. In the present study, the blood glucose concentration at 30 min and the IAUC value of glucose during the postprandial period were higher in the HGI trial than that in the LGI trial, which were consistent with the estimated GI values of two snack bars. "
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    ABSTRACT: Purpose: To investigate the effect of the glycemic index (GI) of pre-exercise snack bars on substrate utilization during subsequent moderate intensity exercise. Methods: Fourteen male participants (Age: 27 ± 5 yr; BMI: 22.5 ± 2.7 kg m(-2); [Formula: see text]: 48.7 ± 6.1 mL kg(-1 )min(-1)) completed two trials in a randomized and counterbalanced crossover design. Two iso-caloric snack bars with different GI values (20, LGI versus 68, HGI) were provided to the participants. Ninety minutes later, all participants completed 45 minutes of ergometer cycling at 65% [Formula: see text]. Substrate utilization was measured using indirect calorimetry. Results: During exercise, higher fat oxidation and lower carbohydrate (CHO) oxidation were observed in the LGI trial (LGI versus HGI: CHO, 87.3 ± 20.1 versus 99.2 ± 19.0 g, p < 0.05; Fat, 15.0 ± 5.8 versus 9.7 ± 7.0 g, p < 0.05). Conclusion: Compared with an iso-caloric HGI snack bar, pre-exercise LGI snack bar consumption may facilitate a shift of substrate utilization from CHO to fat during subsequent moderate intensity exercise.
    International Journal of Food Sciences and Nutrition 08/2013; 64(8). DOI:10.3109/09637486.2013.825701 · 1.21 Impact Factor
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    • "In contrast, plasma insulin concentration increased from 1.9 ± 0.4 μIU/L to 10.5 ± 3.1 μIU/L (P < 0.05) by 2 hr and to 7.6 ± 2.0 μIU/L (P < 0.05) by 6 hr in response to the saury meal and returned to the basal level by the end of the study (Figure 5b). It has been well documented that insulin plays a crucial physiological role in postprandial glucose homeostasis and in inhibiting adipose tissue lipolysis, which may lead to reduced release of fatty acids into the blood stream [16,17]. Thus, the hyperinsulinemia after the saury meal may have caused the observed acute decreases in plasma glucose and free fatty acids. "
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    ABSTRACT: Background Saury oil contains considerable amounts of n-3 polyunsaturated fatty acids (PUFA) and monounsaturated fatty acids (MUFA) with long aliphatic tails (>18C atoms). Ingestion of saury oil reduces the risk of developing metabolic syndrome concomitant with increases in n-3 PUFA and long-chain MUFA in plasma and organs of mice. We therefore evaluated changes in postprandial plasma fatty acid levels and plasma parameters in healthy human subjects after ingestion of a single meal of saury. Findings Five healthy human adults ingested 150 g of grilled saury. Blood was collected before the meal and at 2, 6, and 24 hr after the meal, and plasma was prepared. Plasma levels of eicosapentaenoic acid, docosahexaenoic acid, and long-chain MUFA (C20:1 and C22:1 isomers combined) increased significantly throughout the postprandial period compared with the pre-meal baseline. Postprandial plasma insulin concentration increased notably, and plasma levels of glucose and free fatty acids decreased significantly and subsequently returned to the pre-meal levels. Conclusions Our study suggests that a single saury meal may alter the postprandial plasma levels of n-3 PUFA and long-chain MUFA in healthy human subjects.
    Lipids in Health and Disease 11/2012; 11(1):151. DOI:10.1186/1476-511X-11-151 · 2.22 Impact Factor
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