The hypothalamus bridges the gap between physiology and biochemistry in high-fat diet-induced hepatic insulin resistance.

Abstract

The mechanisms of insulin resistance differ among tissues, and under various circumstances. A high-fat diet is known to induce insulin resistance, but the timing of this insulin resistance induction in the liver differs from that in other insulin-target tissues. Hyperinsulinemic-euglycemic clamp studies have revealed that a high-fat diet induces insulin resistance in the liver relatively quickly, while taking more time in muscle and adipose tissue. In contrast, biochemical studies have shown a high-fat diet to paradoxically enhance insulin signaling in the liver. The results of a recent study conducted by our group indicate that hypothalamic insulin resistance via p70 S6 kinase 1 (S6K1) activation induced by a high-fat diet may explain this discrepancy between physiological and biochemical observations. There are both direct and indirect pathways by which insulin suppresses hepatic glucose production, and the indirect pathway via the hypothalamus is particularly impaired under relatively short-term overfeeding conditions, which in turn leads to compensatory enhancement of insulin signaling in the liver.

• Authors: Hiraku Ono
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 8 Issue 18 Pg. 2885-7 (Sep 15 2009) ISSN: 1551-4005 [Electronic] United States
• PMID: 19738432 (Publication Type: Journal Article, Review)

Chemical References

• Dietary Fats
• Ribosomal Protein S6 Kinases
• Rps6kb1 protein, rat

Topics

• Animals
• Dietary Fats (toxicity)
• Hypothalamus (metabolism)
• Insulin Resistance (physiology)
• Liver (metabolism)
• Rats
• Ribosomal Protein S6 Kinases (metabolism)
• Signal Transduction