Octreotide alleviates obesity by reducing intestinal glucose absorption and inhibiting low-grade inflammation.
OBJECTIVE
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.
Division of Peptides Related with Human Disease, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China. lrui60@yahoo.com.cn
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R
Liu
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Wei
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Guo
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Qiang
X
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Li
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Ou
W
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Huang
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Tang
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D004063:Digestion / Q000187:drug effects; D005765:Gastrointestinal Agents / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D007583:Jejunum / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008871:Microvilli / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D009765:Obesity / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015282:Octreotide / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D051269:Sodium-Glucose Transporter 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013004:Somatostatin / Q000097:blood / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015431:Weight Loss / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D019440:Anti-Obesity Agents; D005765:Gastrointestinal Agents; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D014409:Tumor Necrosis Factor-alpha; D013004:Somatostatin; D015282:Octreotide