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. 2011 Mar;60(3):810-8.
doi: 10.2337/db10-0566. Epub 2011 Feb 3.

Diet and gastrointestinal bypass-induced weight loss: the roles of ghrelin and peptide YY

Keval Chandarana  1 , Cigdem Gelegen, Efthimia Karra, Agharul I Choudhury, Megan E Drew, Veronique Fauveau, Benoit Viollet, Fabrizio Andreelli, Dominic J Withers, Rachel L Batterham
Affiliations

Diet and gastrointestinal bypass-induced weight loss: the roles of ghrelin and peptide YY

Keval Chandarana et al. Diabetes. 2011 Mar.

Abstract

Objective: Bariatric surgery causes durable weight loss. Gut hormones are implicated in obesity pathogenesis, dietary failure, and mediating gastrointestinal bypass (GIBP) surgery weight loss. In mice, we determined the effects of diet-induced obesity (DIO), subsequent dieting, and GIBP surgery on ghrelin, peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). To evaluate PYY's role in mediating weight loss post-GIBP, we undertook GIBP surgery in PyyKO mice.

Research design and methods: Male C57BL/6 mice randomized to a high-fat diet or control diet were killed at 4-week intervals. DIO mice underwent switch to ad libitum low-fat diet (DIO-switch) or caloric restriction (CR) for 4 weeks before being killed. PyyKO mice and their DIO wild-type (WT) littermates underwent GIBP or sham surgery and were culled 10 days postoperatively. Fasting acyl-ghrelin, total PYY, active GLP-1 concentrations, stomach ghrelin expression, and colonic Pyy and glucagon expression were determined. Fasting and postprandial PYY and GLP-1 concentrations were assessed 30 days postsurgery in GIBP and sham pair-fed (sham.PF) groups.

Results: DIO progressively reduced circulating fasting acyl-ghrelin, PYY, and GLP-1 levels. CR and DIO-switch caused weight loss but failed to restore circulating PYY to weight-appropriate levels. After GIBP, WT mice lost weight and exhibited increased circulating fasting PYY and colonic Pyy and glucagon expression. In contrast, the acute effects of GIBP on body weight were lost in PyyKO mice. Fasting PYY and postprandial PYY and GLP-1 levels were increased in GIBP mice compared with sham.PF mice.

Conclusions: PYY plays a key role in mediating the early weight loss observed post-GIBP, whereas relative PYY deficiency during dieting may compromise weight-loss attempts.

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Figures

FIG. 1.
FIG. 1.
Effect of HFD on body weight, fasting plasma concentrations of leptin, acyl-ghrelin, total PYY, and active GLP-1. Cohorts of mice were exposed to control diet or HFD for 4, 8, 12, and 16 weeks and then killed in the fasted state. Body weight gain (A), plasma acyl-ghrelin (B), plasma total PYY (C), and plasma active GLP-1 (D) were assessed. Data are expressed as means ± SE. n = 10. *P < 0.05; **P < 0.01; ***P < 0.001 for HFD vs. control diet.
FIG. 2.
FIG. 2.
Effect of dietary modification on body weight, fasting concentrations of leptin, acyl-ghrelin, total PYY, active GLP-1, and stomach expression of Mboat4. DIO mice were randomized to three groups, continued HFD (DIO), switch to control diet (Switch), or calorically restricted (CR), for 4 weeks and then killed after an overnight fast. Body weight (A), plasma leptin (B), plasma acyl-ghrelin (C), stomach Mboat4 expression (D), plasma total PYY (E), and plasma active GLP-1 (F) were assessed. Data are expressed as means ± SE. n = 10. **P < 0.01; ***P < 0.001 vs. DIO; †P < 0.05; ††P < 0.01; †††P < 0.001 vs. control diet.
FIG. 3.
FIG. 3.
Effect of GIBP surgery in WT and PyyKO mice. Male weight-matched DIO WT mice and PyyKO littermates underwent GIBP surgery or sham procedure. Ten days postoperatively mice were killed in the fasted state. Body weight (A), plasma leptin (B), plasma acyl-ghrelin (C), stomach ghrelin expression (D), plasma total PYY (E), colonic Pyy expression (F), plasma active GLP-1 (G), and colonic glucagon expression (H) were evaluated. Data are expressed as means ± SE. *P < 0.05; **P < 0.01; ††P < 0.01. WT.S, n = 7; WT.BP, n = 8; PyyKO.S, n = 8; PyyKO.BP, n = 7.
FIG. 4.
FIG. 4.
Effect of GIBP and sham.PF on body weight and fasting and postprandial concentrations of total PYY and active GLP-1. Male weight-matched DIO mice underwent GIBP surgery or sham procedure. The sham group was then pair-fed (sham.PF) to the GIBP group. Thirty days postsurgery, a tail bleed was taken after an overnight fast and 90 min postprandially. A: Body weight presurgery and 30 days postsurgery. B: Body weight curves in GIBP and sham.PF groups. C: Fasting and postprandial plasma total PYY. D: Plasma fasted and postprandial active GLP-1. Data are expressed as means ± SE. n = 5. ***P < 0.001 vs. sham.PF. BP, bypass.
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