Weight Loss After RYGB Is Independent of and Complementary to Serotonin 2C Receptor Signaling in Male Mice

Carmody, Jill S.; Ahmad, Nadia; Machineni, Sriram; Lajoie, Scott; Kaplan, Lee M.

doi:10.1210/en.2015-1226

Cited by 10 publications

(9 citation statements)

References 37 publications

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“…Others reported that RYGB rats lost additional weight when treated with serotonin 2C-receptor agonists (Carmody et al, 2015), and ate more and gained weight when treated with a melanocortin 3- or 4-receptor antagonist (Mumphrey et al, 2014) and temporarily ate more after a period of food restriction during which they lost additional weight (Lutz and Bueter, 2014). Thus, a variety of eating-control mechanisms remain functional after RYGB in rats and mice.…”

Section: Discussionmentioning

confidence: 99%

RYGB progressively increases avidity for a low-energy, artificially sweetened diet in female rats

et al. 2016

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Weight re-gain within 2 y after Roux-en-Y gastric bypass (RYGB) is significantly associated with increased intake of and cravings for sweet foods. Here we describe a novel model of this late increase in sweet appetite. Ovariectomized RYGB and Sham-operated rats, with or without estradiol treatment, were maintained on Ensure liquid diet and offered an artificially sweetened low-energy diet (ASD) 2 h/d. First, we tested rats more than six months after RYGB. ASD meals were larger in RYGB than Sham rats, whereas Ensure meals were smaller. General physical activity increased during ASD meals in RYGB rats, but not during Ensure meals. Second, new rats were adapted to ASD before surgery, and were then offered ASD again during 4–10 wk following surgery. Estradiol-treated RYGB rats lost the most weight and progressively increased ASD intake to >20 g/2 h in wk 9–10 vs. ~3 g/2 h in Sham rats. Finally, the same rats were then treated with leptin or saline for 8 d. Leptin did not affect body weight, Ensure intake, or activity during meals, but slightly reduced ASD intake in estradiol-treated RYGB rats. Food-anticipatory activity was increased in estradiol-treated RYGB rats during the saline-injection tests. Because increased meal-related physical activity together with larger meals is evidence of hunger in rats, these data suggest that (1) RYGB can increase hunger for a low-energy sweet food in rats and (2) low leptin levels contribute to this hunger, but are not its only cause. This provides a unique rat model for the increased avidity for sweets that is significantly associated with weight recidivism late after RYGB.

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Section: Discussionmentioning

confidence: 99%

RYGB progressively increases avidity for a low-energy, artificially sweetened diet in female rats

et al. 2016

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“…We evaluated wild-type mice that were part of a larger study examining the effects of 5HT2C-receptor on metabolism after RYGB (29). Male C57BL/6J mice (Jackson Labs, Bar Harbor, ME) were placed on a 60% high fat diet (HFD; Research Diets, D12492) at weaning to induce substantial obesity.…”

Section: Methodsmentioning

confidence: 99%

Cortical and trabecular deterioration in mouse models of Roux-en-Y gastric bypass

Carmody

Brooks

et al. 2016

Bone

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Roux-en-Y gastric bypass (RYGB) is a profoundly effective treatment for severe obesity, but results in significant bone loss in patients. Developing a murine model that recapitulates this skeletal phenotype will provide a robust tool with which to study the physiologic mechanisms of this bone loss. We studied adult male C57BL/6J mice who underwent either RYGB or sham operation. Twelve weeks after surgery, we characterized biochemical bone markers (parathyroid hormone, PTH; C-telopeptide, CTX; and type 1 procollagen, P1NP) and bone microarchitectural parameters as measured by microcomputed tomography. RYGB-treated mice had significant trabecular and cortical bone deficits compared with sham-operated controls. Although adjustment for final body weight eliminated observed cortical differences, the trabecular bone volume fraction remained significantly lower in RYGB mice even after weight adjustment. PTH levels were similar between groups, but RYGB mice had significantly higher indices of bone turnover than sham controls. These data demonstrate that murine models of RYGB recapitulate patterns of bone loss and turnover that have been observed in human clinical studies. Future studies that exploit this murine model will help delineate the alterations in bone metabolism and mechanisms of bone loss after RYGB.

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“…Face to these intriguing results, we were led to raise the question of an eventual fecal loss of energy to account for the prolonged body weight loss in absence of prolonged decrease in food intake and its maintenance during food recovery, as observed in ours [30] and others [[9], [10], [11], [12], [13], [14],16,17,19,20,39] studies. Indeed, another common feature of the literature on gastric bypass in mice is that the surgery induces a strong decrease in body weight under high calorie diets, but is pretty ineffective under standard diet conditions [30,37,38].…”

Section: Discussionmentioning

confidence: 86%

“…For example, the role of the melanocortin system was questioned later [18]. This also relates to the eventual implications of various hormones (including gastrointestinal ones but not only) as fibroblast growth factor 21, peptide YY or glucagon-like peptide 1 (GLP-1), or their receptors as leptin receptor, serotonin 2C receptor, GLP-1 receptor, Y2 receptor [[9], [10], [11], [12], [13], [14],16,17,19,20,39], or other receptors putatively involved in RYGB beneficial effects as the bile acid receptor TGR5 or mu-opioid receptors [14,30] that all concluded that the tested hormone or receptor is dispensable for the metabolic effects of gastric bypass in mice.…”

Section: Discussionmentioning

confidence: 99%

“…RYGB induces a substantial and sustained weight loss of up to 30% of starting body weight associated with enhanced postprandial satiation [5,6] and rapid improvement in T2DM, before any weight loss has occurred [7,8]. A lot of work has been undergone to understand the underlying mechanisms of RYGB, especially in relation with the roles of intestinal glucose metabolism, gastrointestinal hormones or gastrointestinal innervation [[9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20]]. However, the results were often negative and/or globally inconsistent (see “Discussion”), which makes that the mechanisms of the benefits of RYGB in energy homeostasis have remained elusive.…”

Section: Introductionmentioning

confidence: 99%

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Metabolic benefits of gastric bypass surgery in the mouse: The role of fecal losses

Barataud

Vily-Petit

Goncalves

et al. 2020

Molecular Metabolism

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ObjectiveRoux-en-Y gastric surgery (RYGB) promotes a rapid and sustained weight loss and amelioration of glucose control in obese patients. A high number of molecular hypotheses were previously tested using duodenal-jejunal bypass (DJB) performed in various genetic models of mice with knockouts for various hormones or receptors. The data were globally negative or inconsistent. Therefore, the mechanisms remained elusive. Intestinal gluconeogenesis is a gut function that has been suggested to contribute to the metabolic benefits of RYGB in obese patients.MethodsWe studied the effects of DJB on body weight and glucose control in obese mice fed a high fat-high sucrose diet. Wild type mice and mice with a genetic suppression of intestinal gluconeogenesis were studied in parallel using glucose- and insulin-tolerance tests. Fecal losses, including excretion of lipids, were studied from the feces recovered in metabolic cages.ResultsDJB induced a dramatic decrease in body weight and improvement in glucose control (glucose- and insulin-tolerance) in obese wild type mice fed a high calorie diet, for 25 days after the surgery. The DJB-induced decrease in food intake was transient and resumed to normal in 7–8 days, suggesting that decreased food intake could not account for the benefits. Total fecal losses were about 5 times and lipid losses 7 times higher in DJB-mice than in control (sham-operated and pair-fed) mice, and could account for the weight loss of mice. The results were comparable in mice with suppression of intestinal gluconeogenesis. There was no effect of DJB on food intake, body weight or fecal loss in lean mice fed a normal chow diet.ConclusionsDJB in obese mice fed a high calorie diet promotes dramatic fecal loss, which could account for the dramatic weight loss and metabolic benefits observed. This could dominate the effects of the mouse genotype/phenotype. Thus, fecal energy loss should be considered as an essential process contributing to the metabolic benefits of DJB in obese mice.

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Weight Loss After RYGB Is Independent of and Complementary to Serotonin 2C Receptor Signaling in Male Mice

Cited by 10 publications

References 37 publications

RYGB progressively increases avidity for a low-energy, artificially sweetened diet in female rats

RYGB progressively increases avidity for a low-energy, artificially sweetened diet in female rats

Cortical and trabecular deterioration in mouse models of Roux-en-Y gastric bypass

Metabolic benefits of gastric bypass surgery in the mouse: The role of fecal losses

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