Grail is a crucial regulator of various biological processes, including the development of T-cell anergy, antiviral innate immune response, and cancer. However, the role of Grail in adipogenesis and obesity remains unclear. Here, we demonstrated that Grail knockdown in vitro leads to a decrease in PPARγ expression, resulting in adipogenesis inhibition. However, Grail overexpression induced the same effects. Grail was shown to interact with PPARγ, targeting it for degradation and modulating its adipogenic activity. PPARγ expression was shown to be considerably reduced in Grail knockout (KO) mice fed normal diet or high-fat diet (HFD). The administration of both normal diet or HFD to Grail KO mice led to lower adipose mass and body weight than those in the wild-type mice. HFD-fed Grail KO mice had improved glucose and insulin tolerance. Taken together, our results indicate that Grail plays a pivotal role in adipogenesis and diet-induced obesity by regulating PPARγ activity.

In obese adults, nonalcoholic fatty liver disease (NAFLD) is accompanied by multiple metabolic dysfunctions. Although upregulated hepatic fatty acid synthesis has been identified as a crucial mediator of NAFLD development, the underlying mechanisms are yet to be elucidated. In this study, we reported upregulated expression of gene related to anergy in lymphocytes (GRAIL) in the livers of humans and mice with hepatic steatosis. Grail ablation markedly alleviated the high-fat diet-induced hepatic fat accumulation and expression of genes related to the lipid metabolism, in vitro and in vivo. Conversely, overexpression of GRAIL exacerbated lipid accumulation and enhanced the expression of lipid metabolic genes in mice and liver cells. Our results demonstrated that Grail regulated the lipid accumulation in hepatic steatosis via interaction with sirtuin 1. Thus, Grail poses as a significant molecular regulator in the development of NAFLD.

AbstractObjectiveElevation of serum high sensitivity C-reactive protein (hs-CRP) level has been demonstrated as a risk factor for varying diseases, as well as a biomarker for predicting recovery after operation of lumber disc herniation. Our objective was to investigate the relationship between serum hs-CRP and sacroiliac (SI) joint inflammation in patients with undifferentiated spondyloarthritis (uSpA).MethodsIn this retrospective study, we enrolled patients with uSpA who underwent hs-CRP testing between January 2007 and September 2013. Serum hs-CRP was analyzed at our central laboratory. All enrolled patients underwent skeletal scintigraphic scan with quantitative sacroiliac measurement.ResultsA total of 29 patients were enrolled with mean age 32.27 years and female:male ratio of 6:23. Pearson’s correlation coefficient showed a significant difference between hs-CRP in serum and SI/S ratio in uSpA, particularly the middle part of the sacroiliac joint, either right side or left side. The significantly high concentration of serum hs-CRP might indicate a systemic inflammatory response to flare-up of the SI joint and might be an indicator of SI inflammation in uSpA.