The Gut and Energy Balance: Visceral Allies in the Obesity Wars

Badman, Michael K.; Flier, Jeffrey S.

doi:10.1126/science.1109951

Cited by 466 publications

(341 citation statements)

References 74 publications

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“…The gut plays a major role in the regulation of eating and energy balance, 16 mainly as a diffuse endocrine organ able to act on the central nervous system and the adipose tissue through a network of hormones, which are able to induce appetite or satiety while stimulating or inhibiting the motor activity of the gastrointestinal tract. Cholecystokinin, 17 ghrelin 18 and PYY peptide 19 levels are related to the fasting-eating cycle and to the motor function of the gastrointestinal tract.…”

Section: Discussionmentioning

confidence: 99%

Treatment of morbid obesity by intraparietogastric administration of botulinum toxin: a randomized, double-blind, controlled study

et al. 2006

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Objective: The stomach is the main target organ for bariatric surgery, but no medical treatment has been developed to increase satiety and decrease food intake via gastric pathways. The aim of our study was to investigate whether or not the intraparietogastric administration of botulinum toxin A (BTX), able to modify the motility patterns of the stomach, could be useful for treatment of obesity. Design: Double blind controlled study. Subjects: Twenty-four morbidly obese patients (mean weight (s.e.m.) 116.174.89 kg, mean body mass index (BMI) 43.671.09 kg/m 2 ) were blindly randomized to receive 200 IU BTX or placebo into the antrum and fundus of the stomach by intraparietal endoscopic administration. Measurements: We evaluated weight loss, BMI changes, satiety score, the maximal gastric capacity for liquids and the gastric emptying time (octanoic acid breath test). Results: The two groups were homogeneous for anthropometric characteristics. Eight weeks after treatment, BTX patients had significantly higher weight loss (1171.09 vs 5.771.1 kg, Po0.001) and BMI reduction (470.36 vs 270.58 kg/m 2 , Po0.001) and a higher satiety score on a visual analogic scale (7.6370.38 vs 4.7270.44, Po0.001) than controls. Furthermore, BTX patients showed a significantly greater reduction in maximal gastric capacity for liquids (266.6748 vs 139731, Po0.001) and a greater prolongation in gastric emptying time ( þ 18.9378 vs À2.276.9 min, Po0.05). No significant side effects or neurophysiologic changes were found. Conclusions: Topical intragastric BTX was effective in reducing food intake and body weight in morbidly obese patients.

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Section: Discussionmentioning

confidence: 99%

Treatment of morbid obesity by intraparietogastric administration of botulinum toxin: a randomized, double-blind, controlled study

et al. 2006

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“…These peripherally derived hormones can act as long-term signals of energy stores or as short-term signals of hunger, satiety and satiation, and are coordinated within central sites to regulate feeding behavior, metabolism and, ultimately, body weight. 1,2 Amylin is co-secreted from pancreatic b-cells with insulin in response to nutrient ingestion. In rodents, acute administration of amylin reduced meal size.…”

Section: Introductionmentioning

confidence: 99%

Antiobesity effects of the β-cell hormone amylin in combination with phentermine or sibutramine in diet-induced obese rats

Roth¹,

Trevaskis²,

Wilson³

et al. 2008

Int J Obes

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Objective: To characterize the interactive effects of amylin with phentermine or sibutramine on food intake, body weight/ composition and gene expression in diet-induced obese (DIO) rats. Design: DIO rats were intraperitoneally injected with a single dose of amylin (10 mg kg À1 ) and/or phentermine (1 mg kg À1 ) or chronically infused with amylin (100 mg kg À1 d À1 ) or vehicle with or without phentermine (0.5-10 mg kg À1 d À1 ) or sibutramine (3 mg kg À1 d À1 ) using two surgically implanted subcutaneous osmotic mini-pumps. Measurements: Twenty-four hour food intake, locomotor activity and components of meal microstructure (meal size, latency, duration and intermeal interval) were measured following acute administration (amylin, phentermine or amylin þ phentermine). Body weight and composition (for amylin and/or sibutramine or phentermine) and metabolism-related gene mRNA expression in the liver (fatty acid synthase, stearoyl-CoA desaturase-1 and carnitine palmitoyltransferase-1) and brown fat (b-adrenergic receptors and uncoupling protein-1) were measured (for amylin and/or phentermine) after sustained infusion (2 weeks). Results: Acute co-administration of amylin (10 mg kg À1 ) and phentermine (1 mg kg À1 ) reduced acute food intake (up to 19 h) more than either monotherapy. In two studies, sustained subcutaneous infusion of amylin for 2 weeks decreased cumulative food intake (22%) and vehicle-corrected body weight gain (B4-8%). Phentermine's anorexigenic (10-17%) and weightreducing effects (B0-5%) were only evident at the highest dose tested (10 mg kg À1 d À1 ). Combination of amylin (100 mg kg À1 d À1 ) and phentermine reduced food intake (30-43%), body weight (8-12%) and adiposity to a greater extent than either monotherapy. Amylin prevented phentermine-induced reductions in UCP-1 mRNA in brown adipose tissue. When amylin þ sibutramine were infused, mathematically additive decreases in food intake (up to 45%) and body weight (up to 12%) were evident. Similar to amylin þ phentermine treatment, amylin þ sibutramine mediated weight loss was attributable to significant reductions in fat mass. Conclusions: Combined treatment of DIO rats with the pancreatic b-cell hormone amylin and phentermine or sibutramine resulted in additive anorexigenic, weight-and fat-reducing effects.

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“…Melanocortin neurons are a critical component of the gut-brain and adipose-brain circuits involved in energy homeostasis, the long term balancing of energy intake and expenditure to maintain body weight at a constant level [2,9]. Neurons secreting the endogenous ligands for melanocortin receptors expressed in the brain are located in the arcuate nucleus of the hypothalamus and the nucleus tractus solitarius in the brainstem [9,14,37].…”

Section: Introductionmentioning

confidence: 99%

A derivative of the melanocortin receptor antagonist SHU9119 (PG932) increases food intake when administered peripherally

Sutton

Babin

et al. 2008

Peptides

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Melanocortin receptors are considered promising candidates for the treatment of behavioral and metabolic disorders ranging from obesity to anorexia and cachexia. These experiments examined the response of mice to peripheral injections of two compounds. PG932 is a derivative of SHU9119 which is non-selective antagonist of melanocortin-3 and melanocortin-4 receptors (Mc3r, Mc4r). PG946 is a derivative of a hybrid of alpha-and beta-MSH, and is a moderately selective Mc3r antagonist. SHU9119 increases food intake when administered intracerebroventricularly but is without effect when injected into the periphery. In contrast, PG932 was found to be highly effective at stimulating food intake when administered peripherally by intraperitoneal injection. The orexigenic effect of PG932 required functional Mc4r, suggesting that inhibition of this receptor is involved in the stimulation of food intake. PG946 did not significantly affect on feeding behavior. PG932 is thus a useful new compound for studies examining the regulation of appetite and energy balance, and may also prove useful for the treatment of cachectic conditions.

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The Gut and Energy Balance: Visceral Allies in the Obesity Wars

Cited by 466 publications

References 74 publications

Treatment of morbid obesity by intraparietogastric administration of botulinum toxin: a randomized, double-blind, controlled study

Treatment of morbid obesity by intraparietogastric administration of botulinum toxin: a randomized, double-blind, controlled study

Antiobesity effects of the β-cell hormone amylin in combination with phentermine or sibutramine in diet-induced obese rats

A derivative of the melanocortin receptor antagonist SHU9119 (PG932) increases food intake when administered peripherally

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