Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are characterized by an increase in hepatic triglyceride content with infiltration of immune cells, which can cause steatohepatitis and hepatic insulin resistance. C-C chemokine receptor 7 (CCR7) is primarily expressed in immune cells, and CCR7 deficiency leads to the development of multi-organ autoimmunity, chronic renal disease and autoimmune diabetes. Here, we investigated the effect of CCR7 on hepatic steatosis in a mouse model and its underlying mechanism. Our results demonstrated that body and liver weights were higher in the CCR7−/− mice than in the wild-type (WT) mice when they were fed a high-fat diet. Further, glucose tolerance and insulin sensitivity were markedly diminished in CCR7−/− mice. The number of invariant natural killer T (iNKT) cells was reduced in the livers of the CCR7−/− mice. Moreover, liver inflammation was detected in obese CCR7−/− mice, which was ameliorated by the adoptive transfer of hepatic mononuclear cells from WT mice, but not through the transfer of hepatic mononuclear cells from CD1d−/− or interleukin-10-deficient (IL-10−/−) mice. Overall, these results suggest that CCR7+ mononuclear cells in the liver could regulate obesity-induced hepatic steatosis via induction of IL-10-expressing iNKT cells.
Meteorin-like (metrnl) is a recently identified adipomyokine that has beneficial effects on glucose metabolism. However, its underlying mechanism of action is not completely understood. In this study, we have shown that a level of metrnl increase in vitro under electrical-pulse-stimulation (EPS) and in vivo in exercise mice, suggesting that metrnl is an exercise-induced myokine. In addition, metrnl increases glucose uptake through the calcium-dependent AMPK pathway. Metrnl also increases the phosphorylation of HDAC5, a transcriptional repressor of GLUT4, in an AMPK-dependent manner. Phosphorylated HDAC5 interacts with 14-3-3 proteins and sequesters them in the cytoplasm, resulting in the activation of GLUT4 transcription. The intraperitoneal injection of recombinant metrnl improves glucose tolerance in mice with high fat-induced obesity or type 2 diabetes (db/db), but this is not seen in AMPK muscle-specific null mice (AMPK MKO). In conclusion, we have demonstrated that metrnl induces beneficial effects on glucose metabolism via AMPK and is a promising therapeutic candidate for glucose-related diseases such as type 2 diabetes. Exercise has the potential to protect against metabolic disease, cardiovascular disease, cancer, and dementia 1 . In response to exercise, skeletal muscle cells secrete various factors called myokines that elicit responses in an auto-, para-, or endocrine manner 2-5 . Myokines are known to improve glucose uptake 6,7 , glucose tolerance 8 , regulation of fat oxidation 8,9 , and satellite cell proliferation 10,11 . Adipose tissue has been established as an endocrine organ that releases various adipokines to control systemic metabolism and energy homeostasis 12,13 .Many contraction-regulated myokines are known to be secreted by adipocytes and are thus called adipomyokines. Adipomyokines are associated with beneficial, exercise-induced metabolic effects [14][15][16] . We have analyzed adipomyokines such as irisin 17 , fstl-1 18 , resistin 19 , and visfatin 20 . Our findings support the notion that these secreted molecules might mediate some of the well-established, beneficial effects of exercise.Meteorin-like hormone (metrnl), also known as cometin, subfatin, or IL-39, is a secreted adipomyokine 21,22 . Metrnl is expressed in various tissues, including liver, heart, stromal cells, macrophages, spleen, and central nervous system (CNS) tissues 23,24 . Metrnl expression is increased in white adipose tissue during acute cold exposure, and in muscle tissue after acute bouts of exercise 25 . Metrnl is also known to induce the expression of genes associated with thermogenesis in brown/beige adipocytes, where it stimulates anti-inflammatory cytokines 25 .While the expression and function of metrnl have been explored extensively in fat tissues, the studies on the molecular mechanism of metrnl in skeletal muscle are lacking.AMP-activated kinase (AMPK) is a master regulator of metabolic homeostasis and an energy-sensing serine/threonine kinase that is activated when cellular energy levels are l...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.