Gastroenterology

Gastroenterology

Volume 138, Issue 7, June 2010, Pages 2426-2436.e3
Gastroenterology

Basic—Alimentary Tract
Sleeve Gastrectomy Induces Loss of Weight and Fat Mass in Obese Rats, but Does Not Affect Leptin Sensitivity

https://doi.org/10.1053/j.gastro.2010.02.059Get rights and content

Background & Aims

Surgical intervention produces sustainable weight loss and metabolic improvement in obese individuals. Vertical sleeve gastrectomy (VSG) produces dramatic, sustained weight loss; we investigated whether these changes result from improved sensitivity to leptin.

Methods

VSG was performed in Long–Evans rats with diet-induced obesity. Naïve or sham-operated rats, fed either ad libitum or pair-fed with the VSG group, were used as controls. Following surgery, body weights and food intake were monitored. We investigated energy expenditure, meal patterns, leptin sensitivity, and expression of pro-opiomelanocortin/agouti-related peptide/neuropeptide Y in the hypothalamus of the rats.

Results

We observed sustained losses in weight and body fat in male and female rats after VSG. Weight loss persisted after the disappearance of a transient, postsurgical food intake reduction. Resting energy expenditure was similar between control and VSG rats. VSG rats maintained their reduced body weights. However, they responded to a chronic food restriction challenge by overeating, which resulted in prerestriction, rather than pre-VSG, body weights. Consistent with lower adiposity, VSG decreased plasma leptin levels. Although VSG slightly improved leptin's anorectic action, the response was comparable to that observed in controls matched for adiposity by caloric restriction. Changes in hypothalamic neuropeptide expression were consistent with the lower body weight and lower leptin levels but cannot account for the sustained weight loss.

Conclusions

VSG causes sustained reduction in body weight, which results from loss of fat mass. The maintenance of weight loss observed did not result from changes in sensitivity to leptin.

Section snippets

Animals

Male and female Long–Evans rats (Harlan Laboratories, Indianapolis, IN; 250–300 g) were fed either a high-fat butter oil-based diet (HFD; Research Diets, New Brunswick, NJ, D12451; 45% fat; 4.73 kcal/g) or standard chow (Harlan-Teklad, Indianapolis, IN) for 8 weeks prior to surgery. Rats were housed at the University of Cincinnati at the Metabolic Diseases Institute under controlled conditions (12:12-hour light–dark cycle, 50%–60% humidity, 25°C with free access to water and food except where

Weight Loss and Fat Mass Loss Following VSG Persist Despite Transient Reductions in Food Intake

Following surgery, VSG rats lost about 20% of initial weight (Figure 1A and B). After the initial period of weight loss (10 days), VSG animals gained an average of 1.03 ± 0.11 g/day for males and 1.63 ± 0.14 g/day for females. This is comparable to weight gain in both naïve (females: 1.12 ± 0.05 g/day, males: 1.54 ± 0.14 g/day) and sham animals (females: 1.43 ± 0.10 g/day, males: 1.57 ± 0.11 g/day). Body weight remained reduced in VSG rats compared to sham and naïve rats throughout the duration

Discussion

The current rat model of VSG produces significant and durable weight loss in obese male and female rats. Importantly, this rodent model of VSG leads the rat to defend a new, lower body weight. Unlike what is seen following weight loss by caloric restriction, rats following VSG do not overeat to compensate for this reduced fat mass. Additionally, we provide strong evidence that the weight loss cannot be attributed to an improvement in leptin sensitivity.

Weight loss secondary to VSG was due to

References (21)

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Conflicts of interest These authors disclose the following:

Drs Seeley, Tschöp, Woods, and Sandoval receive funding from Johnson & Johnson.

The remaining authors disclose no conflicts.

Funding This work was supported by National Institutes of Health grants DK54890 and DK083870 and Ethicon Endo-Surgery. MAS is also supported by T32 GM063483.

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