Increased oxidative stress precedes the onset of high-fat diet-induced insulin resistance and obesity.

Abstract

Insulin resistance is a key pathophysiological feature of metabolic syndrome. However, the initial events triggering the development of insulin resistance and its causal relations with dysregulation of glucose and fatty acids metabolism remain unclear. We investigated biological pathways that have the potential to induce insulin resistance in mice fed a high-fat diet (HFD). We demonstrate that the pathways for reactive oxygen species (ROS) production and oxidative stress are coordinately up-regulated in both the liver and adipose tissue of mice fed an HFD before the onset of insulin resistance through discrete mechanism. In the liver, an HFD up-regulated genes involved in sterol regulatory element binding protein 1c-related fatty acid synthesis and peroxisome proliferator-activated receptor alpha-related fatty acid oxidation. In the adipose tissue, however, the HFD down-regulated genes involved in fatty acid synthesis and up-regulated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. Furthermore, increased ROS production preceded the elevation of tumor necrosis factor-alpha and free fatty acids in the plasma and liver. The ROS may be an initial key event triggering HFD-induced insulin resistance.

• Authors: Naoto Matsuzawa-Nagata, Toshinari Takamura, Hitoshi Ando, Seiji Nakamura, Seiichiro Kurita, Hirofumi Misu, Tsuguhito Ota, Masayoshi Yokoyama, Masao Honda, Ken-ichi Miyamoto, Shuichi Kaneko
• Journal: Metabolism: clinical and experimental (Metabolism) Vol. 57 Issue 8 Pg. 1071-7 (Aug 2008) ISSN: 1532-8600 [Electronic] United States
• PMID: 18640384 (Publication Type: Journal Article)

Chemical References

• Blood Glucose
• Dietary Fats
• Insulin
• RNA, Messenger
• Reactive Oxygen Species

Topics

• Adipose Tissue (metabolism)
• Animals
• Blood Glucose (metabolism)
• Body Weight (physiology)
• Dietary Fats (administration & dosage)
• Glucose Tolerance Test
• Insulin (blood)
• Insulin Resistance (physiology)
• Liver (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Obesity (metabolism)
• Oxidative Stress (physiology)
• RNA, Messenger (biosynthesis, genetics)
• Reactive Oxygen Species (metabolism)
• Up-Regulation