Arachidonic Acid Can Significantly Prevent Early Insulin Resistance Induced by a High-Fat Diet

Abstract

Aim: To investigate whole-body metabolic disorder and hepatic glucose output (HGO) disturbance in rats with insulin resistance induced by a short-term high-fat diet, and the effect of arachidonic acid (AA). Methods: Twenty-four normal male Wistar rats (230–250 g) were randomly divided into 3 groups according to their weight and fed for 12 weeks: control group, n = 8, fed with standard chow diet; high-fat (HF) group, n = 8, fed with a high-fat diet; HF+AA group, n = 8, fed with a high-fat diet and administered orally 3 mg·kg^–1·day^–1AA. Results: Early insulin resistance was successfully induced in HF-fed rats with hyperinsulinemia (p < 0.05), higher plasma triglyceride (TG) (p < 0.05), higher fasting liver glycogen content (p < 0.01) and higher glucose-insulin index (p < 0.01) during an oral glucose tolerance test (OGTT). The AA treatment significantly decreased the glucose-insulin index (p < 0.01), blood TG (p < 0.05) and glycogen content (p < 0.05) in liver. Both activity of phosphoenolpyruvate carboxykinase (PEPCK) (p < 0.05) and mRNA levels of PEPCK (p < 0.05) and glucose-6-phosphatase (G-6-Pase) (p < 0.01) in liver were also observed to be significantly decreased. But there were significant differences in the glucose-insulin index (p < 0.01) during OGTT, and glycogen content (p < 0.01) between the HF+AA and control groups. Conclusion: AA can significantly prevent whole-body insulin resistance induced by a high-fat diet, as well as accompanied HGO disturbance in the overnight fasting state, but not thoroughly.

The Effects of Palmitate on Hepatic Insulin Resistance Are Mediated by NADPH Oxidase 3-derived Reactive Oxygen Species through JNK and p38MAPK Pathways

“…It is known that increased hepatic gluconeogenesis is induced by overexpression of PEPCK, a key gluconeogenic enzyme, and the catalytic subunit glucose-6-phosphatase, which is regulated by transcriptional and nontranscriptional mechanisms (46,47). PEPCK catalyzes one of the rate-limiting steps of gluconeogenesis, the reaction of oxaloacetic acid to phosphoenolpyruvate, contributing to increased hepatic glucose output and elevated blood glucose levels in the initial stages of type 2 diabetes characterized by insulin resistance (48). Expression of PEPCK is regulated by Akt and FOXO1.…”

Insulin resistance in the liver: Deficiency or excess of insulin?

“…12,13 Hence, insulin resistance often is accompanied by increased circulating levels of insulin. [14][15][16] If this compensatory rise in insulin production is not maintained by the pancreas, causing insulin levels to drop, then type 2 diabetes ensues. [17][18][19] Questions Raised by Insulin Resistance…”

Hepatic glucose production pathways after three days of a high-fat diet

“…Glucose over-production after longer durations was attributed to increased gluconeogenesis, but interestingly increased hepatic glycogen levels were also observed in rats after a 2-week high-fat diet [34, 35]. Longer high-fat diets also increased PEPCK expression [16, 36] and induced the citric acid cycle intermediates such as fumarate and citrate in liver of mice [37]. These changes were not observed in current study, but there are some similarity between current study and studies with longer high-fat diets.…”

“…It is also worth emphasizing that flux through specific pathways may not correlate closely with expression of the putative controlling enzymes [15]. For example, up-regulation of phospho enol pyruvate carboxykinase (PEPCK) expression after a 12-week high-fat diet [16] may not mean the same degree of PEPCK flux or not even glucose production. Burgess et al reported that substantial reduction of hepatic PEPCK contents caused only small changes in the flux through PEPCK [17].…”