Adipose Tissue, Inflammation, and Cardiovascular Disease

Berg, Anders H.; Scherer, Philipp E.

doi:10.1161/01.res.0000163635.62927.34

Cited by 1,791 publications

(1,398 citation statements)

References 147 publications

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“…Obesity is now widely recognised to be associated with a heightened inflammatory state involving elevations in the circulating levels and production of inflammatory cytokines such as C-reactive protein, IL-6 and TNF-α [32]. Moreover, two separate reports have shown that adipose tissue is characterised by macrophage infiltration, which could affect its normal function and inflammatory properties [33,34].…”

Section: Discussionmentioning

confidence: 99%

Identification of ALOX5 as a gene regulating adiposity and pancreatic function

et al. 2008

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Aims/hypothesis We previously used an integrative genetics approach to demonstrate that 5-lipoxygenase (5-LO) deficiency in mice (Alox5 −/− ) protects against atherosclerosis despite increasing lipid levels and fat mass. In the present study, we sought to further examine the role of 5-LO in adiposity and pancreatic function. Methods Alox5 −/− and wild-type (WT) mice were characterised with respect to adiposity and glucose/insulin metabolism using in vivo and in vitro approaches. The role of ALOX5 in pancreatic function in human islets was assessed through short interfering RNA (siRNA) knockdown experiments. Results Beginning at 12 weeks of age, Alox5 −/− mice had significantly increased fat mass, plasma leptin levels and fasting glucose levels, but lower fasting insulin levels (p< 0.05). Although Alox5 −/− mice did not exhibit insulin resistance, they had impaired insulin secretion in response to a bolus glucose injection. Histological analyses revealed Diabetologia (2008) that Alox5 −/− mice had increased islet area, beta cell nuclear size, and numbers of beta cells/mm 2 islet (p < 0.05), indicative of both hyperplasia and hypertrophy. Basal and stimulated insulin secretion in isolated Alox5 −/− islets were significantly lower than in WT islets (p <0.05) and accompanied by a three-to fivefold decrease in the expression of the genes encoding insulin and pancreatic duodenal homeobox 1 (Pdx1). Direct perturbation of ALOX5 in isolated human islets with siRNA decreased insulin and PDX1 gene expression by 50% and insulin secretion by threefold (p<0.05). Conclusions/interpretation These results provide strong evidence for pleiotropic metabolic effects of 5-LO on adiposity and pancreatic function and may have important implications for therapeutic strategies targeting this pathway for the treatment of cardiovascular disease.

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Section: Discussionmentioning

confidence: 99%

Identification of ALOX5 as a gene regulating adiposity and pancreatic function

et al. 2008

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“…In addition, the proinflammatory cytokines, which is increased with aging, are involved in insulin action (Sepe, Tchkonia, Thomou, Zamboni, & Kirkland, 2011). Adiponectin is also a metabolic regulator that can be linked to aging due to its effect on insulin sensitivity (Berg & Scherer, 2005). Meanwhile, aging is strongly associated with a progressive loss in mitochondrial function (Dirks, Hofer, Marzetti, Pahor, & Leeuwenburgh, 2006).…”

Section: Lifestyle Associations and Interventions For Aging And Admentioning

confidence: 99%

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

et al. 2018

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Alzheimer's disease is the most prevalent cause of dementia, which is defined by the combined presence of amyloid and tau, but researchers are gradually moving away from the simple assumption of linear causality proposed by the original amyloid hypothesis. Aging is the main risk factor for Alzheimer's disease that cannot be explained by amyloid hypothesis. To evaluate how aging and Alzheimer's disease are intrinsically interwoven with each other, we review and summarize evidence from molecular, cellular, and system level. In particular, we focus on study designs, treatments, or interventions in Alzheimer's disease that could also be insightful in aging and vice versa.

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“…These suggest that perivascular adipocytes modulate insulin sensitivity and cellular function in an autocrine or paracrine manner while attracting macrophages to the depot, further exacerbating inflammation and adipocyte dysfunction (20,21).…”

Section: Pathophysiologymentioning

confidence: 99%