Acute ω-3 Fatty Acid Enrichment Selectively Reverses High-Saturated Fat Feeding-Induced Insulin Hypersecretion But Does Not Improve Peripheral Insulin Resistance

Abstract

In rats fed a high-saturated fat diet, replacement of a small percentage of total fatty acids with long-chain -3 fatty acids from fish oil for the duration of high-fat feeding prevents the development of insulin resistance. We investigated the effect of acute (24-h) modulation of dietary fat composition on glucose-stimulated insulin secretion (GSIS) in rats made insulin resistant by highsaturated fat feeding for 4 weeks. Insulin secretion after an intravenous glucose challenge was greatly increased by high-saturated fat feeding. Glucose tolerance was minimally perturbed, demonstrating insulin hypersecretion compensated for insulin resistance. The effect of high-saturated fat feeding to enhance GSIS was retained in perifused islets, such that glucose stimulus-secretion coupling was potentiated. Acute replacement of 7% of dietary fatty acids with long-chain -3 fatty acids reversed insulin hypersecretion in vivo, and the effect of long-term high-saturated fat feeding to enhance insulin secretion by perifused islets was also completely reversed. Although a hyperbolic relationship existed between insulin secretion and action in the high-saturated fat and control groups, lowered insulin secretion in the acute fish oil-supplemented group was not accompanied by improved insulin action, and glucose tolerance was adversely affected. Our studies are important because they demonstrate that hyperinsulinemia can be rapidly reversed via the dietary provision of small amounts of long-chain -3 fatty acids. However, this "insulin sparing" action of acute dietary long-chain -3 fatty acids occurs in the absence of an acute improvement in insulin sensitivity and therefore at the expense of maintenance of glucose tolerance. Diabetes 53 (Suppl. 1)

Lipid, Glycemic, and Insulin Responses to Meals Rich in Saturated,cis-Monounsaturated, and Polyunsaturated (n-3 and n-6) Fatty Acids in Subjects With Type 2 Diabetes

“…Although we also found an increased postprandial insulin response with palmitic acid compared with oleic acid, our observation of higher insulin response to linoleic acid than to oleic acid is not consistent with the data of Stein et al (34). Holness et al (35) reported that acute replacement of some dietary saturated fatty acids with EPA and DHA, in rats made insulin resistant by high-saturated fat feeding for 4 weeks, reversed insulin hypersecretion in vivo and during glucose perifusion of isolated islets. The lowered insulin secretion, however, was not accompanied by improved insulin action, and glucose tolerance was adversely affected.…”

High-fat diet based on dried bovine brain: an effective animal model of dyslipidemia and insulin resistance

“…As such, SFA-rich diets, when compared with polyunsaturated fatty acid diets, are known to cause glucose intolerance and to increase insulin resistance [2]. Additionally, previous studies reported that the consumption of SFA had an insulinogenic effect [13,24]. This effect appears to be related to the increase in intracellular calcium concentration in the pancreatic islets, which consequently augmented the insulin release [45].…”

Molecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis

“…This "repartitioning" contributed to their rather beneficial effects, such as reduction of blood serum levels of VLDL, triacylglycerols, and cholesterol and decrease of insulin resistance (de Lorgeril and Salen, 2006). Other positive treatment effect of n-3 PUFAs has been related to their interference with insulinotropic effects of saturated fatty acids, lowering insulin-dependent stimulation of lipogenic genes in the liver (Holness et al, 2004). PUFA-mediated activation of PPAR␣ was demonstrated to antagonize detrimental effects on pancreatic ␤-cells in vitro, being able to rescue ␤-cell function (Holness et al, 2007) and advantageous effects of PUFA supplementation in steatosis were suggested to result from an improvement of peripheral insulin resistance, which was demonstrated in vitro but not supported by findings in vivo (Fickova et al, 1998;Ryan et al, 2000;Holness et al, 2004).…”

“…Other positive treatment effect of n-3 PUFAs has been related to their interference with insulinotropic effects of saturated fatty acids, lowering insulin-dependent stimulation of lipogenic genes in the liver (Holness et al, 2004). PUFA-mediated activation of PPAR␣ was demonstrated to antagonize detrimental effects on pancreatic ␤-cells in vitro, being able to rescue ␤-cell function (Holness et al, 2007) and advantageous effects of PUFA supplementation in steatosis were suggested to result from an improvement of peripheral insulin resistance, which was demonstrated in vitro but not supported by findings in vivo (Fickova et al, 1998;Ryan et al, 2000;Holness et al, 2004). Finally, another putative protection mechanism of unsaturated fatty acids in steatosis and steatohepatitis was attributed to their antioxidant effects, serving as a cellular reservoir for undue lipid peroxidation (Davis et al, 2006;Oliveira et al, 2006).…”