Effects of sleeve gastrectomy in high fat diet-induced obese mice: respective role of reduced caloric intake, white adipose tissue inflammation and changes in adipose tissue and ectopic fat depots
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Sleeve gastrectomy (SG) has become a popular bariatric procedure. The mechanisms responsible for weight loss and improvement of metabolic disturbances have still not been completely elucidated. We investigated the effect of SG on body weight, adipose tissue depots, glucose tolerance, and liver steatosis independent of reduced caloric intake in high-fat-diet-induced obese mice.
C57BI/6 J mice fed a high fat diet (45 %) for 33 weeks were divided into three groups: sleeve gastrectomy (SG, 13 mice), sham-operated ad libitum fed (SALF, 13 mice) and sham-operated pair fed (PFS, 13 mice). The animals were humanely killed 23 days after surgery.
In SG mice, food intake was reduced transiently, but weight loss was significant and persistent compared to controls (SG vs. PFS, P < 0.05; PFS vs. SALF, P < 0.05). SG mice showed improved glucose tolerance and lower levels of liver steatosis compared with controls (area under the curve, SG vs. PFS, P < 0.01; PFS vs. SALF, P < 0.05) (liver steatosis, SG vs. PFS, P < 0.05; PFS vs. SALF, P < 0.01). This was associated with a decrease in the ratios of the weight of pancreas, epididymal and inguinal adipose tissues to body weight, and an increase in the ratio of brown adipose tissue weight to body weight. Epididymal adipose tissue was also infiltrated by fewer activated T cells and by more anti-inflammatory regulatory T cells. Serum levels of fasting acyl ghrelin were still significantly decreased 3 weeks after surgery in SG mice compared to PFS mice (P < 0.05).
Reduced white adipose tissue inflammation, modification of adipose tissue development (brown vs. white adipose tissue), and ectopic fat are potential mechanisms that may account for the reduced caloric intake independent effects of SG.
KeywordsBariatric surgery Glucose tolerance Morbid obesity Sleeve gastrectomy Weight loss
This work was supported by grants from INSERM (France), the University of Nice, the Programme Hospitalier de Recherche Clinique (Centre Hospitalier Universitaire of Nice), and charities (Association Française pour l’Etude du Foie (AFEF)/Schering-Plough to PG, EFSD/Lilly European Diabetes Research Programme to PG and la Fondation pour la Recherche Médicale to Jean-Louis Nahon). We thank Dr. Jean-Louis Nahon for scientific discussions, Dr. M. C. Brahimi-Horn for editorial work, and the members of the INSERM U1065 animal facility.
Stéphanie Patouraux was supported by the Fondation pour la Recherche Médicale. Philippe Gual is a recipient of an Interface Grant from the Centre Hospitalier Universitaire of Nice. Anne-Sophie Schneck, Antonio Iannelli, Déborah Rousseau, Stéphanie Bonnafous, Beatrice Bailly-Maitre, Ophélia Le Thuc, Carole Rovere, Patricia Panaia-Ferrari, Rodolphe Anty, Albert Tran, and Jean Gugenheim have no conflicts of interest or financial ties to disclose.
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