Defective NOD2 peptidoglycan sensing promotes diet-induced inflammation, dysbiosis, and insulin resistance
نویسندگان
چکیده
Pattern recognition receptors link metabolite and bacteria-derived inflammation to insulin resistance during obesity. We demonstrate that NOD2 detection of bacterial cell wall peptidoglycan (PGN) regulates metabolic inflammation and insulin sensitivity. An obesity-promoting high-fat diet (HFD) increased NOD2 in hepatocytes and adipocytes, and NOD2(-/-) mice have increased adipose tissue and liver inflammation and exacerbated insulin resistance during a HFD. This effect is independent of altered adiposity or NOD2 in hematopoietic-derived immune cells. Instead, increased metabolic inflammation and insulin resistance in NOD2(-/-) mice is associated with increased commensal bacterial translocation from the gut into adipose tissue and liver. An intact PGN-NOD2 sensing system regulated gut mucosal bacterial colonization and a metabolic tissue dysbiosis that is a potential trigger for increased metabolic inflammation and insulin resistance. Gut dysbiosis in HFD-fed NOD2(-/-) mice is an independent and transmissible factor that contributes to metabolic inflammation and insulin resistance when transferred to WT, germ-free mice. These findings warrant scrutiny of bacterial component detection, dysbiosis, and protective immune responses in the links between inflammatory gut and metabolic diseases, including diabetes.
منابع مشابه
NOD1 Activators Link Innate Immunity to Insulin Resistance
OBJECTIVE Insulin resistance associates with chronic inflammation, and participatory elements of the immune system are emerging. We hypothesized that bacterial elements acting on distinct intracellular pattern recognition receptors of the innate immune system, such as bacterial peptidoglycan (PGN) acting on nucleotide oligomerization domain (NOD) proteins, contribute to insulin resistance. RE...
متن کاملLong-term dysbiosis promotes insulin resistance during obesity despite rapid diet-induced changes in the gut microbiome of mice
متن کامل
Give a NOD to insulin resistance.
INSULIN RESISTANCE IS A LEADING CAUSE of type 2 diabetes, and inflammation has emerged as an important mediator between obesity and insulin resistance. The links between immunity and metabolism are extensive and have been proposed to originate from structures in lower organisms that are responsible for both danger and metabolite sensing (6). This has introduced the interesting concept that comm...
متن کاملInnate Immunity: ER Stress Recruits NOD1 and NOD2 for Delivery of Inflammation
NOD1 and NOD2, two members of the intracellular NOD-like receptor family, sense bacterial peptidoglycan-derived fragments and induce pro-inflammatory responses. Recent work provides evidence for a role for NOD1/NOD2 signaling in mediating ER-stress-induced inflammatory responses via a peptidoglycan-independent mechanism.
متن کاملEffect of S-Methyl-L-Cysteine on Oxidative Stress, Inflammation and Insulin Resistance in Male Wistar Rats Fed with High Fructose Diet
Background: S-methyl cysteine (SMC) is a hydrophilic cysteine-containing compound naturally found in garlic and onion. The purpose of the present study was to investigate the protective effect of SMC on oxidative stress, inflammation and insulin resistance in an experiment of metabolic syndrome.Methods: Male Wistar rats were divided into five groups (6 rats in each group), namely; control, cont...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 7 شماره
صفحات -
تاریخ انتشار 2015