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- Hassing, H. C., et al.
(författare)
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SULF2 Strongly Prediposes to Fasting and Postprandial Triglycerides in Patients with Obesity and Type 2 Diabetes Mellitus
- 2014
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 22:5, s. 1309-1316
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Hepatic overexpression of sulfatase-2 (SULF2), a heparan sulfate remodeling enzyme, strongly contributes to high triglyceride (TG) levels in obese, type 2 diabetic (T2DM) db/db mice. Nevertheless, data in humans are lacking. Here, the association of human hepatic SULF2 expression and SULF2 gene variants with TG metabolism in patients with obesity and/or T2DM was investigated. Methods: Liver biopsies from 121 obese subjects were analyzed for relations between hepatic SULF2 mRNA levels and plasma TG. Associations between seven SULF2 tagSNPs and TG levels were assessed in 210 obese T2DM subjects with dyslipidemia. Replication of positive findings was performed in 1,316 independent obese T2DM patients. Postprandial TRL clearance was evaluated in 29 obese T2DM subjects stratified by SULF2 genotype. Results: Liver SULF2 expression was significantly associated with fasting plasma TG (r = 0.271; P = 0.003) in obese subjects. The SULF2 rs2281279(A>G) SNP was reproducibly associated with lower fasting plasma TG levels in obese T2DM subjects (P < 0.05). Carriership of the minor G allele was associated with lower levels of postprandial plasma TG (P < 0.05) and retinyl esters levels (P < 0.001). Conclusions: These findings implicate SULF2 as potential therapeutic target in the atherogenic dyslipidemia of obesity and T2DM.
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- Khan, M. T., et al.
(författare)
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Microbial Modulation of Insulin Sensitivity
- 2014
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 20:5, s. 753-760
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Tidskriftsartikel (refereegranskat)abstract
- The gut microbiota has emerged as an integral factor that impacts host metabolism and has been suggested to play a vital role in metabolic diseases such as obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. In humans, cross-sectional studies have identified microbiota profiles associated with metabolic diseases, whereas causation mainly has been demonstrated in animal models. Recent studies involving microbiota-based interventions in humans, or transfer of disease-associated microbiota into germ-free mice, underscore that an altered microbiota may directly modulate host metabolism in humans. However, it will be essential to determine whether an altered gut microbiota precedes development of insulin resistance and diabetes and to identify the underlying molecular mechanisms. Increased mechanistic insights of how the microbiota modulates metabolic disease in humans may pave the way for identification of innovative microbiota-based diagnostics and/or therapeutics.
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- Nieuwdorp, Max, et al.
(författare)
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Role of the microbiome in energy regulation and metabolism
- 2014
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Ingår i: Gastroenterology. - : W.B. Saunders. - 0016-5085 .- 1528-0012. ; 146:6, s. 1525-1533
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Tidskriftsartikel (refereegranskat)abstract
- Intestinal microbes regulate metabolic function and energy balance; an altered microbial ecology is believed to contribute to the development of several metabolic diseases. Relative species abundance and metabolic characteristics of the intestinal microbiota change substantially in those who are obese or have other metabolic disorders and in response to ingested nutrients or therapeutic agents. The mechanisms through which the intestinal microbiota and its metabolites affect host homeostasis are just beginning to be understood. We review the relationships between the intestinal microbiota and host metabolism, including energy intake, use, and expenditure, in relation to glucose and lipid metabolism. These associations, along with interactions among the intestinal microbiota, mucus layer, bile acids, and mucosal immune responses, reveal potential mechanisms by which the microbiota affect metabolism. We discuss how controlled studies involving direct perturbations of microbial communities in human and animal models are required to identify effective therapeutic targets in the microbiota. © 2014 by the AGA Institute.
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- Udayappan, S. D., et al.
(författare)
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Intestinal microbiota and faecal transplantation as treatment modality for insulin resistance and type 2 diabetes mellitus
- 2014
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 177:1, s. 24-29
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Forskningsöversikt (refereegranskat)abstract
- The prevalence of obesity and diabetes mellitus type 2 is increasing rapidly around the globe. Recent insights have generated an entirely new perspective that the intestinal microbiota may play a significant role in the development of these metabolic disorders. Alterations in the intestinal microbiota composition promote systemic inflammation that is a hallmark of obesity and subsequent insulin resistance. Thus, it is important to understand the reciprocal relationship between intestinal microbiota composition and metabolic health in order to eventually prevent disease progression. In this respect, faecal transplantation studies have implicated that butyrate-producing intestinal bacteria are crucial in this process and be considered as key players in regulating diverse signalling cascades associated with human glucose and lipid metabolism.
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