Gastroenterology

Gastroenterology

Volume 141, Issue 3, September 2011, Pages 939-949.e4
Gastroenterology

Original Research
Basic and Translational—Alimentary Tract
Sleeve Gastrectomy in Rats Improves Postprandial Lipid Clearance by Reducing Intestinal Triglyceride Secretion

https://doi.org/10.1053/j.gastro.2011.05.008Get rights and content

Background & Aims

Postprandial hyperlipidemia is a risk factor for atherosclerotic heart disease and is associated with the consumption of high-fat diets and obesity. Bariatric surgeries result in superior and more durable weight loss than dieting. These surgeries are also associated with multiple metabolic improvements, including reduced plasma lipid levels. We investigated whether the beneficial effects of vertical sleeve gastrectomy (VSG) on plasma lipid levels are weight independent.

Methods

VSG was performed on Long-Evans rats with diet-induced obesity. Controls were sham-operated animals who were either pair-fed or ad libitum-fed. We measured fasting and postprandial levels of plasma lipid. To determine hepatic and intestinal triglyceride secretion, we injected the lipase inhibitor poloxamer 407 alone or before oral lipid gavage. 13C-Triolein was used to estimate postprandial uptake of lipid in the intestine.

Results

Rats that received VSG and high-fat diets had markedly lower fasting levels of plasma triglyceride, cholesterol, and phospholipid than obese and lean (pair-fed) controls that were fed high-fat diets. Rats that received VSG had a marked, weight-independent reduction in secretion of intestinal triglycerides. VSG did not alter total intestinal triglyceride levels or size of the cholesterol storage pool nor did it affect the expression of genes in the intestine that control triglyceride metabolism and synthesis. VSG did not affect fasting secretion of triglyceride, liver weight, hepatic lipid storage, or transcription of genes that regulate hepatic lipid processing.

Conclusions

VSG reduced postprandial levels of plasma lipid, independently of body weight. This resulted from reduced intestinal secretion of triglycerides following ingestion of a lipid meal and indicates that VSG has important effects on metabolism.

Section snippets

Animals

Male Long-Evans rats (Harlan Laboratories, Indianapolis, IN; 250–300 g) were fed 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 and maintained on this diet postsurgery. Rats were housed under controlled conditions (12:12-hour light-dark cycle, 50%–60% humidity, 25°C, free access to water and food except where noted). A subgroup of sham-operated rats was

VSG Reduces Plasma Lipids

Four-hour fasting plasma lipids were measured 50 days postsurgery, when rats were weight-stable. Obese, ad libitum-fed sham-operated (SHAM) animals were heavier compared with VSG, sham-operated, chow-fed (CHOW), and sham-operated, PF groups (Figure 1A). Weight loss after VSG is a selective loss of fat mass (Stefater et al18 and Figure 1B). All animals in PF, SHAM, and VSG groups were maintained on HFD for the duration of the study. Plasma cholesterol (Figure 1C, P < .001), triglycerides (Figure

Discussion

It has been speculated that plasma lipids are reduced in humans after bariatric surgery in part because of conscious dietary changes. Here, we show that the improvement to lipid homeostasis after VSG is instead a physiologic consequence of the surgery. We report lower plasma lipid levels in VSG-operated rats than weight-matched (PF) rats despite the fact that both groups were maintained on the same amount of HFD.

Our data show that plasma triglyceride levels are markedly reduced in VSG-operated

Acknowledgments

The authors thank Elizabeth Parks and Rohit Kohli for providing valuable advice in designing these studies; Jose Berger, Mouhamadoul Toure, Ken Parks, and Kathi Smith for their surgical expertise; and Michelle Kirby and Therese Rider for technical assistance with biochemical assays.

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    Conflicts of interest These authors disclose the following: Randy J. Seeley: Johnson & Johnson (Ethicon Endo-Surgery), Zafgen, Merck, Pfizer, Mannkind, Roche. Darleen A. Sandoval: Johnson & Johnson. The remaining authors disclose no conflicts.

    Funding Supported by NIH grants DK54890 and DK083870 and Ethicon Endo-Surgery.

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