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Erschienen in: European Journal of Nutrition 3/2013

01.04.2013 | Original Contribution

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

verfasst von: R. Liu, N. Wei, W. Guo, O. Qiang, X. Li, Y. Ou, W. Huang, C. W. Tang

Erschienen in: European Journal of Nutrition | Ausgabe 3/2013

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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.
Literatur
1.
Zurück zum Zitat Van der Merwe MT (2009) Obesity in women-a life cycle of medical risk. JEMDSA 14:139–142 Van der Merwe MT (2009) Obesity in women-a life cycle of medical risk. JEMDSA 14:139–142
2.
Zurück zum Zitat Livhits M, Mercado C, Yermilov I, Parikh JA, Dutson E, Mehran A, Ko CY, Gibbons MM (2010) Behavioral factors associated with successful weight loss after gastric bypass. Am Surg 76:1139–1142 Livhits M, Mercado C, Yermilov I, Parikh JA, Dutson E, Mehran A, Ko CY, Gibbons MM (2010) Behavioral factors associated with successful weight loss after gastric bypass. Am Surg 76:1139–1142
3.
Zurück zum Zitat Atkinson RL (2005) Management of obesity: pharmacotherapy. In: Kopelman PG, Caterson LD, Dietz WH (eds) Clinical obesity in adults and children. Blackwell, Malden, pp 380–393CrossRef Atkinson RL (2005) Management of obesity: pharmacotherapy. In: Kopelman PG, Caterson LD, Dietz WH (eds) Clinical obesity in adults and children. Blackwell, Malden, pp 380–393CrossRef
4.
Zurück zum Zitat Cordido F, Isidro ML (2010) Approved and off-label uses of obesity medications and potential new pharmacologic treatment options. Pharmaceuticals 3:125–145CrossRef Cordido F, Isidro ML (2010) Approved and off-label uses of obesity medications and potential new pharmacologic treatment options. Pharmaceuticals 3:125–145CrossRef
5.
Zurück zum Zitat Lustig RH, Hinds PS, Ringwald-Smith K, Christensen RK, Kaste SC, Schreiber RE, Rai SN, Lensing SY, Wu S, Xiong X (2003) Octreotide therapy of pediatric hypothalamic obesity: a double-blind, placebo-controlled trial. J Clin Endocrinol Metab 88:2586–2592CrossRef Lustig RH, Hinds PS, Ringwald-Smith K, Christensen RK, Kaste SC, Schreiber RE, Rai SN, Lensing SY, Wu S, Xiong X (2003) Octreotide therapy of pediatric hypothalamic obesity: a double-blind, placebo-controlled trial. J Clin Endocrinol Metab 88:2586–2592CrossRef
6.
Zurück zum Zitat Caesar R, Fåk F, Bäckhed F (2010) Effects of gut microbiota on obesity and atherosclerosis via modulation of inflammation and lipid metabolism. J Intern Med 268:320–328CrossRef Caesar R, Fåk F, Bäckhed F (2010) Effects of gut microbiota on obesity and atherosclerosis via modulation of inflammation and lipid metabolism. J Intern Med 268:320–328CrossRef
7.
Zurück zum Zitat Muccioli GG, Naslain D, Bäckhed F, Reigstad CS, Lambert DM, Delzenne NM, Cani PD (2010) The endocannabinoid system links gut microbiota to adipogenesis. Mol Syst Biol 6:392CrossRef Muccioli GG, Naslain D, Bäckhed F, Reigstad CS, Lambert DM, Delzenne NM, Cani PD (2010) The endocannabinoid system links gut microbiota to adipogenesis. Mol Syst Biol 6:392CrossRef
8.
Zurück zum Zitat Brignardello J, Morales P, Diaz E, Romero J, Brunser O, Gotteland M (2010) Pilot study: alterations of intestinal microbiota in obese humans are not associated with colonic inflammation or disturbances of barrier function. Aliment Pharmacol Ther 32:1307–1314CrossRef Brignardello J, Morales P, Diaz E, Romero J, Brunser O, Gotteland M (2010) Pilot study: alterations of intestinal microbiota in obese humans are not associated with colonic inflammation or disturbances of barrier function. Aliment Pharmacol Ther 32:1307–1314CrossRef
10.
Zurück zum Zitat Dyer J, Daly K, Salmon KS, Arora DK, Kokrashvili Z, Margolskee RF, Shirazi-Beechey SP (2007) Intestinal glucose sensing and regulation of intestinal glucose absorption. Biochem Soc Trans 35:1191–1194CrossRef Dyer J, Daly K, Salmon KS, Arora DK, Kokrashvili Z, Margolskee RF, Shirazi-Beechey SP (2007) Intestinal glucose sensing and regulation of intestinal glucose absorption. Biochem Soc Trans 35:1191–1194CrossRef
11.
Zurück zum Zitat Ahlman H, Nilsson O (2001) The gut as the largest endocrine organ in the body. Ann Oncol 12(Suppl 2):S63–S68CrossRef Ahlman H, Nilsson O (2001) The gut as the largest endocrine organ in the body. Ann Oncol 12(Suppl 2):S63–S68CrossRef
12.
Zurück zum Zitat Tang C, Lan C, Wang CH, Liu R (2005) Alleviation of multiple organ dysfunction syndrome by somatostatin via suppression of intestinal mucosal mast cells. Shock 23:470–475CrossRef Tang C, Lan C, Wang CH, Liu R (2005) Alleviation of multiple organ dysfunction syndrome by somatostatin via suppression of intestinal mucosal mast cells. Shock 23:470–475CrossRef
13.
Zurück zum Zitat Wu H, Liu L, Tan QH, Wang CH, Guo MM, Xie YM, Tang CW (2009) Somatostatin limits intestinal ischemia-reperfusion injury in macaques via suppression of TLR4–NF-κB cytokine pathway. J Gastrointestinal Surg 13:983–993CrossRef Wu H, Liu L, Tan QH, Wang CH, Guo MM, Xie YM, Tang CW (2009) Somatostatin limits intestinal ischemia-reperfusion injury in macaques via suppression of TLR4–NF-κB cytokine pathway. J Gastrointestinal Surg 13:983–993CrossRef
14.
Zurück zum Zitat Pintér E, Helyes Z, Szolcsányi J (2006) Inhibitory effect of somatostatin on inflammation and nociception. Pharmacol Ther 112:440–456CrossRef Pintér E, Helyes Z, Szolcsányi J (2006) Inhibitory effect of somatostatin on inflammation and nociception. Pharmacol Ther 112:440–456CrossRef
15.
Zurück zum Zitat Csaba Z, Dournaud P (2001) Cellular biology of somatostatin receptors. Neuropeptides 35:1–23CrossRef Csaba Z, Dournaud P (2001) Cellular biology of somatostatin receptors. Neuropeptides 35:1–23CrossRef
16.
Zurück zum Zitat Guo MM, Tan QH, Fan H, Huang MH, Wang CH, Qiu XQ, Tang CW (2005) Changes of somatostatin and expression of somatostatin receptor in small intestine and liver tissues during macaque development. Acta Physiol Sin 57:719–724 Guo MM, Tan QH, Fan H, Huang MH, Wang CH, Qiu XQ, Tang CW (2005) Changes of somatostatin and expression of somatostatin receptor in small intestine and liver tissues during macaque development. Acta Physiol Sin 57:719–724
17.
Zurück zum Zitat Hodin RA, Saldinger P, Meng S (1995) Small bowel adaptation: counter regulatory effects of epidermal growth factor and somatostatin on the program of early gene expression. Surgery 118:206–210; discussion 210–211CrossRef Hodin RA, Saldinger P, Meng S (1995) Small bowel adaptation: counter regulatory effects of epidermal growth factor and somatostatin on the program of early gene expression. Surgery 118:206–210; discussion 210–211CrossRef
18.
Zurück zum Zitat Wang ZX, Chen JW, Zhou YK (2002) An experimental study of the effects of octreotide on small intestinal mucosa in rats. J Math Med 15:125–127 (article in Chinese) Wang ZX, Chen JW, Zhou YK (2002) An experimental study of the effects of octreotide on small intestinal mucosa in rats. J Math Med 15:125–127 (article in Chinese)
19.
Zurück zum Zitat Silva AP, Bethmann K, Raulf F, Schmid HA (2005) Regulation of ghrelin secretion by somatostatin analogs in rats. Eur J Endocrinol 152:887–894CrossRef Silva AP, Bethmann K, Raulf F, Schmid HA (2005) Regulation of ghrelin secretion by somatostatin analogs in rats. Eur J Endocrinol 152:887–894CrossRef
20.
Zurück zum Zitat Kang L, Routh VH, Kuzhikandathil EV, Kuzhikandathil EV, Gaspers LD, Levin BE (2004) Physiological and molecular characteristics of rat hypothalamic ventromedial nucleus glucosensing neurons. Diabetes 53:549–559CrossRef Kang L, Routh VH, Kuzhikandathil EV, Kuzhikandathil EV, Gaspers LD, Levin BE (2004) Physiological and molecular characteristics of rat hypothalamic ventromedial nucleus glucosensing neurons. Diabetes 53:549–559CrossRef
21.
Zurück zum Zitat Hotamisligil GS, Erbay E (2008) Nutrient sensing and inflammation in metabolic diseases. Nat Rev Immunol 8:923–934CrossRef Hotamisligil GS, Erbay E (2008) Nutrient sensing and inflammation in metabolic diseases. Nat Rev Immunol 8:923–934CrossRef
22.
Zurück zum Zitat Shoelson SE, Goldfine AB (2009) Getting away from glucose: fanning the flames of obesity-induced inflammation. Nat Med 15:373–374CrossRef Shoelson SE, Goldfine AB (2009) Getting away from glucose: fanning the flames of obesity-induced inflammation. Nat Med 15:373–374CrossRef
23.
Zurück zum Zitat Kern PA, Ranganathan S, Li C, Wood L, Ranganathan G (2001) Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab 280:E745–E751 Kern PA, Ranganathan S, Li C, Wood L, Ranganathan G (2001) Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab 280:E745–E751
24.
Zurück zum Zitat Syrenicz A, Garanty-Bogacka B, Syrenicz M, Gebala A, Walczak M (2006) Low grade systemic inflammation and the risk of type 2 diabetes in obese children and adolescents. Neuro Endocrinol Lett 27:453–458 Syrenicz A, Garanty-Bogacka B, Syrenicz M, Gebala A, Walczak M (2006) Low grade systemic inflammation and the risk of type 2 diabetes in obese children and adolescents. Neuro Endocrinol Lett 27:453–458
25.
Zurück zum Zitat Panagiotakos DB, Pitsavos C, Yannakoulia M, Chrysohoou C, Stefanadis C (2005) The implication of obesity and central fat on markers of chronic inflammation: the ATTICA study. Atherosclerosis 183:308–315CrossRef Panagiotakos DB, Pitsavos C, Yannakoulia M, Chrysohoou C, Stefanadis C (2005) The implication of obesity and central fat on markers of chronic inflammation: the ATTICA study. Atherosclerosis 183:308–315CrossRef
26.
Zurück zum Zitat Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB (2001) Low grade systemic inflammation in overweight children. Pediatrics 107:E13CrossRef Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB (2001) Low grade systemic inflammation in overweight children. Pediatrics 107:E13CrossRef
27.
Zurück zum Zitat Dandona P, Weinstock R, Thusu K, Abdel-Rahman E, Aljada A (1998) Tumor necrosis factor-alpha in sera of obese patients: fall with weight loss. J Clin Endocrinol Metab 83:2907–2910CrossRef Dandona P, Weinstock R, Thusu K, Abdel-Rahman E, Aljada A (1998) Tumor necrosis factor-alpha in sera of obese patients: fall with weight loss. J Clin Endocrinol Metab 83:2907–2910CrossRef
28.
Zurück zum Zitat Lee YH, Pratley RE (2005) The evolving role of inflammation in obesity and the metabolic syndrome. Curr Diab Rep 5:70–75CrossRef Lee YH, Pratley RE (2005) The evolving role of inflammation in obesity and the metabolic syndrome. Curr Diab Rep 5:70–75CrossRef
29.
Zurück zum Zitat Zhou C, Li J, Wang HY, Tang CW (2009) Decreased somatostatin is related to the hypersensitivity of intestinal epithelia to LPS via up–regulated TLR4–TBK1 pathway in rats chronically exposed to ethanol. Alcohol 43:293–303CrossRef Zhou C, Li J, Wang HY, Tang CW (2009) Decreased somatostatin is related to the hypersensitivity of intestinal epithelia to LPS via up–regulated TLR4–TBK1 pathway in rats chronically exposed to ethanol. Alcohol 43:293–303CrossRef
30.
Zurück zum Zitat Joshi MS, Crouser ED, Julian MW, Schanbacher BL, Bauer JA (2000) Digital imaging analysis for the study of endotoxin-induced mitochondrial ultrastructure injury. Anal Cell Pathol 21:41–48 Joshi MS, Crouser ED, Julian MW, Schanbacher BL, Bauer JA (2000) Digital imaging analysis for the study of endotoxin-induced mitochondrial ultrastructure injury. Anal Cell Pathol 21:41–48
31.
Zurück zum Zitat Rosensweig NS (1975) Diet and intestinal enzyme adaptation: implications for gastrointestinal disorders. Am J Clin Nutr 28:648–655 Rosensweig NS (1975) Diet and intestinal enzyme adaptation: implications for gastrointestinal disorders. Am J Clin Nutr 28:648–655
32.
Zurück zum Zitat Ferraris RP, Villenas SA, Diamond J (1992) Regulation of brush-border enzyme activities and enterocyte migration rates in mouse small intestine. Am J Physiol Gastrointest Liver Physiol 262:G1047–G1059 Ferraris RP, Villenas SA, Diamond J (1992) Regulation of brush-border enzyme activities and enterocyte migration rates in mouse small intestine. Am J Physiol Gastrointest Liver Physiol 262:G1047–G1059
33.
Zurück zum Zitat Black BL, Croom J, Eisen EJ, Petro AE, Edwards CL, Surwit RS (1998) Differential effects of fat and sucrose on body composition in A/J and C57BL/6 mice. Metabolism 47:1354–1359CrossRef Black BL, Croom J, Eisen EJ, Petro AE, Edwards CL, Surwit RS (1998) Differential effects of fat and sucrose on body composition in A/J and C57BL/6 mice. Metabolism 47:1354–1359CrossRef
34.
Zurück zum Zitat Hediger MA, Rhoads DB (1994) Molecular physiology of sodium glucose cotransporters. Physiol Rev 74:993–1026 Hediger MA, Rhoads DB (1994) Molecular physiology of sodium glucose cotransporters. Physiol Rev 74:993–1026
35.
Zurück zum Zitat Lee JY, Hannun YA, Obeid LM (2000) Functional dichotomy of protein kinase C (PKC) in tumor necrosis factor-a (TNF-α) signal transduction in L929 cells. J Biol Chem 275:29290–29298CrossRef Lee JY, Hannun YA, Obeid LM (2000) Functional dichotomy of protein kinase C (PKC) in tumor necrosis factor-a (TNF-α) signal transduction in L929 cells. J Biol Chem 275:29290–29298CrossRef
Metadaten
Titel
Octreotide alleviates obesity by reducing intestinal glucose absorption and inhibiting low-grade inflammation
verfasst von
R. Liu
N. Wei
W. Guo
O. Qiang
X. Li
Y. Ou
W. Huang
C. W. Tang
Publikationsdatum
01.04.2013
Verlag
Springer-Verlag
Erschienen in
European Journal of Nutrition / Ausgabe 3/2013
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-012-0413-6

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