Metabolic surgery for type 2 diabetes

Ahn, Soo Min; Pomp, Alfons; Rubino, Francesco

doi:10.1111/j.1749-6632.2011.05984.x

Cited by 18 publications

(11 citation statements)

References 85 publications

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“…Surgical reorganization of the gastrointestinal tract not only results in sustained weight loss but also changes the metabolic physiology beyond diet restriction and malabsorption, leading toward improved glucose homeostasis and insulin sensitivity (2,43,49). It is also well known that increased energy expenditure and fat utilization through neuroendocrine and nutrient signaling are enhanced with gastric bypass surgery (30,34,35,37,43,44).…”

Section: Discussionmentioning

confidence: 97%

Pharmacological inhibition to examine the role of DGAT1 in dietary lipid absorption in rodents and humans

Maciejewski

LaPerle

Chen

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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Alterations in fat metabolism, in particular elevated plasma concentrations of free fatty acids and triglycerides (TG), have been implicated in the pathogenesis of Type 2 diabetes, obesity, and cardiovascular disease. Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), a member of the large family of membrane-bound O-acyltransferases, catalyzes the final step in triacylglycerol formation. In the intestine, DGAT1 is one of the acyltransferases responsible for the reesterficiation of dietary TG. Following a single dose of a selective pharmacological inhibitor of DGAT1, PF-04620110, a dose-dependent inhibition of TG and vitamin A absorption postprandially was demonstrated in rodents and human subjects. In C57/BL6J mice, acute DGAT1 inhibition alters the temporal and spatial pattern of dietary lipid absorption. To understand the impact of DGAT1 inhibition on enterocyte lipid metabolism, lipomic profiling was performed in rat intestine and plasma as well as human plasma. DGAT1 inhibition causes an enrichment of polyunsaturated fatty acids within the TG class of lipids. This pharmacological intervention gives us insight as to the role of DGAT1 in human dietary lipid absorption.

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Section: Discussionmentioning

confidence: 97%

Pharmacological inhibition to examine the role of DGAT1 in dietary lipid absorption in rodents and humans

Maciejewski

LaPerle

Chen

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Gastric bypass surgery is frequently associated with complete remission of type II diabetes, although the rapid timeframe of improved insulin sensitivity frequently precedes significant weight loss (69, 70). Strikingly, reduced adipose macrophage density and decreased stromal vascular fraction expression of factors responsible for macrophage recruitment have been observed in subcutaneous white adipose tissue of patients 3 months after gastric bypass surgery (8).…”

Section: Clinical-translational Advancesmentioning

confidence: 99%

Molecular Pathways: Adipose Inflammation as a Mediator of Obesity-Associated Cancer

Howe

Subbaramaiah

Hudis

et al. 2013

Clinical Cancer Research

287

237

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The increasing rate of obesity worldwide is predicted to be associated with a surge in diseases. Notably, obesity has been linked to approximately 20% of cancer cases in the United States; obesity is associated with both increased risk and worse outcomes after diagnosis. Altered levels of circulating factors are strongly implicated including insulin, insulin-like growth factor 1, leptin, adiponectin and interleukin-6 (IL-6). Additionally, increasing attention has focused on the consequences of local adipose inflammation. Inflammatory foci characterized by crown-like structures consisting of dead adipocytes encircled by macrophages occur in white adipose depots, including the breast tissue, of most overweight and obese women. Saturated fatty acids, released as a consequence of obesity-associated lipolysis, induce macrophage activation via Toll-like receptor 4, thereby stimulating NFκB signaling. This, in turn, activates transcription of proinflammatory genes including cyclooxygenase-2, IL-6, IL-1β, and tumor necrosis factor α. Elevated levels of proinflammatory mediators cause both local and systemic effects. Of particular relevance with regard to breast cancer is increased transcription of the CYP19 gene encoding aromatase, the rate-limiting enzyme for estrogen synthesis. Notably, this obesity-inflammation-aromatase axis provides a plausible explanation for increased rates of post-menopausal, hormone receptor-positive breast cancer associated with obesity and hence may offer targets for interventions to attenuate risk or improve prognosis. Potential approaches include weight reduction, exercise, and suppression of obesity-driven signaling pathways using pharmaceutical or dietary agents. A key future goal is to identify biomarkers that accurately report adipose inflammation, both for identification of at-risk individuals and to assess the efficacy of interventions.

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“…In obese subjects undergoing Roux-en-Y gastric bypass (RYGB) surgery, metabolic improvements can be observed in the first week after the surgery, preceding significant weight loss (Ahn et al, 2011; Rubino et al, 2004). These weight-independent metabolic improvements may be mediated by rapid changes in microbiota composition since major reconstruction of the gastrointestinal tract as part of gastric bypass significantly alters the microbiota shortly after the surgery (Graessler et al, 2012; Li et al, 2011).…”

Section: Energy Extraction From Foodmentioning

confidence: 99%

Pathways in Microbe-Induced Obesity

2013

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Diet, host gene composition, and alterations in the intestinal microbiota can contribute to obesity. In microbe-induced obesity, metabolic changes stem from primary perturbation of the microbiota, consequent to modern changes in human biology. Microbiota disruption during early development can result in syndromes of metabolic dysfunction. We focus on the pathways involved in these interactions, particularly related to energy extraction and the role of inflammation in the metabolic phenotypes. Model physiologic systems and perturbations including gastric bypass surgery, pregnancy, and hibernation provide insight into the respective roles of the critical participants.

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Metabolic surgery for type 2 diabetes

Cited by 18 publications

References 85 publications

Pharmacological inhibition to examine the role of DGAT1 in dietary lipid absorption in rodents and humans

Pharmacological inhibition to examine the role of DGAT1 in dietary lipid absorption in rodents and humans

Molecular Pathways: Adipose Inflammation as a Mediator of Obesity-Associated Cancer

Pathways in Microbe-Induced Obesity

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