Octreotide alleviates obesity by reducing intestinal glucose absorption and inhibiting low-grade inflammation

Eur J Nutr. 2013 Apr;52(3):1067-75. doi: 10.1007/s00394-012-0413-6. Epub 2012 Jul 18.

Abstract

Purpose: To investigate the role of octreotide, a somatostatin (SST) analog with anti-inflammatory effects, on the digestive and absorptive functions of jejunum in rats fed a high-fat diet, as well as its therapeutic prospects for diet-induced obesity.

Methods: Rats were divided into three groups with different diet and treatment for the 176-day experiment: (1) control, 18 rats fed with standard chow, (2) high-fat control, 19 rats fed with high-fat chow, and (3) high-fat octreotide, 21 rats fed with high-fat chow and treated with octreotide for the last 8 days of the experiment. Plasma tumor necrosis factor-α (TNF-α) was measured by ELISA and SST by radioimmunoassay. Disaccharidase activity in the jejunal homogenate was determined. SST and Na⁺-dependent glucose transporter 1 (SGLT-1) in the jejunal mucosa were visualized by immunohistochemistry. SGLT-1 was quantified by reverse transcription polymerase chain reaction and Western blot assays.

Results: After 176 days, the fat/body weight ratio, villus height, maltase, SGLT-1, and plasma TNF-α in the high-fat control rats were much higher than those in the control rats (p < 0.01 or p < 0.05) and were significantly lower in the high-fat + octreotide rats (p < 0.01 or p < 0.05). SST levels were dramatically different in the intestinal mucosa of the two high-fat groups (231.12 ± 98.18 pg/mg in the high-fat controls and 480.01 ± 286.65 pg/mg in the octreotide group).

Conclusions: The low-grade inflammation induced by high-fat diet apparently reduced the secretion of intestinal SST, which increased intestinal absorption of energy and nutrients and formation of adipose tissues. Octreotide effectively reversed this process, a finding that has far-reaching significance for the regulation of energy balance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Anti-Obesity Agents / therapeutic use*
  • Digestion / drug effects
  • Gastrointestinal Agents / therapeutic use
  • Gene Expression Regulation / drug effects
  • Intestinal Absorption / drug effects*
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / ultrastructure
  • Jejunum / drug effects*
  • Jejunum / immunology
  • Jejunum / metabolism
  • Jejunum / ultrastructure
  • Male
  • Microvilli / drug effects
  • Microvilli / immunology
  • Microvilli / metabolism
  • Microvilli / ultrastructure
  • Obesity / drug therapy*
  • Obesity / immunology
  • Obesity / metabolism
  • Obesity / pathology
  • Octreotide / therapeutic use*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Sodium-Glucose Transporter 1 / antagonists & inhibitors
  • Sodium-Glucose Transporter 1 / genetics
  • Sodium-Glucose Transporter 1 / metabolism
  • Somatostatin / blood
  • Somatostatin / metabolism
  • Tumor Necrosis Factor-alpha / blood
  • Weight Loss / drug effects

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Anti-Obesity Agents
  • Gastrointestinal Agents
  • Slc5a1 protein, rat
  • Sodium-Glucose Transporter 1
  • Tumor Necrosis Factor-alpha
  • Somatostatin
  • Octreotide