Abstract
The contribution of dietary fat content and type to changes in the sensitivity of hepatic lipid metabolism to insulin was studied in primary hepatocyte cultures from donor rats maintained on a low-fat diet (LF), or on diets enriched in olive oil (OO) or fish oil (FO). The higher rate of fatty acid oxidation in hepatocytes from the FO-fed group was resistant to the inhibitory effects of insulin observed in hepatocytes from the other groups. Insulin stimulation of fatty acid incorporation into triglyceride (TG) was also less pronounced in hepatocytes from the FO-fed group than in those from the OO-fed group but there was no difference in the stimulatory effect of insulin on fatty acid incorporation into phospholipid (PL) in these two groups. In the case of fatty acid incorporation into both PL and TG, hepatocytes from the LF group were refractory to stimulation by insulin. At each concentration of insulin, hepatocytes from the FO-fed group secreted less very low density lipoprotein (VLDL) TG than those from the other groups. However, the absolute suppression of VLDL TG secretion by insulin was similar irrespective of the diet of the donor animals.We conclude that chronic consumption of a particuar type of dietary fat does not affect the insulin sensitivity of the major pathways of hepatic lipid metabolism in a consistent manner.—Baker, P. W., and G. F. Gibbons. Effect of dietary fish oil on the sensitivity of hepatic lipid metabolism to regulation by insulin. J. Lipid Res. 2000. 41: 719–726.
Highlights
The contribution of dietary fat content and type to changes in the sensitivity of hepatic lipid metabolism to insulin was studied in primary hepatocyte cultures from donor rats maintained on a low-fat diet (LF), or on diets enriched in olive oil (OO) or fish oil (FO)
We have used hepatocytes from rats fed diets rich in olive oil (OO) or fish oil (FO) to Abbreviations: VLDL, very low density lipoprotein; apo, apolipoprotein; TG, triglyceride; PL, phospholipid; NEFA, non-esterified fatty acids; DGAT, diacylglycerol acyltransferase; CoA, coenzyme A; CPT-I, carnitine palmitoyltransferase I; acetylCoA carboxylase (ACC), acetyl-CoA carboxylase; DG, diacylglycerol; EPA, eicosapentaenoic acid
Significant relationships were observed between plasma insulin and TG (P Ͻ 0.02; r2 ϭ 0.43) and plasma insulin and NEFA (P Ͻ 0.001; r2 ϭ 0.67) with the FO-fed group being intermediate between the LF- and OO-fed groups (Table 1)
Summary
The contribution of dietary fat content and type to changes in the sensitivity of hepatic lipid metabolism to insulin was studied in primary hepatocyte cultures from donor rats maintained on a low-fat diet (LF), or on diets enriched in olive oil (OO) or fish oil (FO). High dietary intakes of certain fatty acids, such as those found in olive oil, result in severe insulin resistance [10, 11] Isocaloric substitution of these fatty acids with fish oil, protect against insulin resistance [10, 12] and reduce VLDL secretion Primary cultures of hepatocytes retain for some time the metabolic characteristics of the donor animals [15] For this reason, we have used hepatocytes from rats fed diets rich in olive oil (OO) or fish oil (FO) to Abbreviations: VLDL, very low density lipoprotein; apo, apolipoprotein; TG, triglyceride; PL, phospholipid; NEFA, non-esterified fatty acids; DGAT, diacylglycerol acyltransferase; CoA, coenzyme A; CPT-I, carnitine palmitoyltransferase I; ACC, acetyl-CoA carboxylase; DG, diacylglycerol; EPA, eicosapentaenoic acid
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