The effect of bariatric surgery on serum TRAIL and osteoprotegerin levels in obesity complicated by glucose disorders

Samaras, Katherine; Morris, Margaret J.; Lord, Reginald V.; Kavurma, Mary M.

doi:10.1016/j.clnme.2014.09.004

Cited by 1 publication

(1 citation statement)

References 31 publications

(32 reference statements)

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“…Collectively, our study implies that TRAIL improves insulin sensitivity by modulating expression of genes involved in glucose metabolism and insulin signaling. Consistent with this, plasma TRAIL levels in T2D patients after gastric banding surgery were increased and correlated with improved β-cell function 35 . TNF ligand regulation of insulin signaling and glucose homeostasis may in fact be a common theme in diabetics, since TNF-α and FasL have also been implicated in insulin resistance 36 , 37 .…”

Section: Discussionsupporting

confidence: 73%

Non-alcoholic fatty liver disease, vascular inflammation and insulin resistance are exacerbated by TRAIL deletion in mice

Cartland

Harith

Genner

et al. 2017

Sci Rep

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Non-alcoholic fatty liver disease (NAFLD) incorporates steatosis, non-alcoholic steato-hepatitis (NASH) and liver cirrhosis, associating with diabetes and cardiovascular disease (CVD). TNF-related apoptosis-inducing ligand (TRAIL) is protective of CVD. We aimed to determine whether TRAIL protects against insulin resistance, NAFLD and vascular injury. Twelve-week high fat diet (HFD)-fed Trail −/− mice had increased plasma cholesterol, insulin and glucose compared to wildtype. Insulin tolerance was impaired with TRAIL-deletion, with reduced p-Akt, GLUT4 expression and glucose uptake in skeletal muscle. Hepatic triglyceride content, inflammation and fibrosis were increased with TRAIL-deletion, with elevated expression of genes regulating lipogenesis and gluconeogenesis. Moreover, Trail −/− mice exhibited reduced aortic vasorelaxation, impaired insulin signaling, and >20-fold increased mRNA expression for IL-1β, IL-6, and TNF-α. In vitro, palmitate treatment of hepatocytes increased lipid accumulation, inflammation and fibrosis, with TRAIL mRNA significantly reduced. TRAIL administration inhibited palmitate-induced hepatocyte lipid uptake. Finally, patients with NASH had significantly reduced plasma TRAIL compared to control, simple steatosis or obese individuals. These findings suggest that TRAIL protects against insulin resistance, NAFLD and vascular inflammation. Increasing TRAIL levels may be an attractive therapeutic strategy, to reduce features of diabetes, as well as liver and vascular injury, so commonly observed in individuals with NAFLD.

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Section: Discussionsupporting

confidence: 73%