Microbiota and adipocyte mitochondrial damage in type 2 diabetes are linked by Mmp12+ macrophages.

Autor:	Li Z; Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR.; Shanghai Mengniu Biotechnology R&D Co., Ltd., Shanghai, China., Gurung M; Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR., Rodrigues RR; College of Pharmacy, Oregon State University, Corvallis, OR.; Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.; Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, MD., Padiadpu J; College of Pharmacy, Oregon State University, Corvallis, OR., Newman NK; College of Pharmacy, Oregon State University, Corvallis, OR., Manes NP; Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD., Pederson JW; Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR., Greer RL; Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR., Vasquez-Perez S; Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR., You H; Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR., Hioki KA; College of Pharmacy, Oregon State University, Corvallis, OR., Moulton Z; Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR., Fel A; Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD., De Nardo D; Anatomy and Developmental Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Australia., Dzutsev AK; Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD., Nita-Lazar A; Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD., Trinchieri G; Laboratory of Integrative Cancer Immunology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD., Shulzhenko N; Carlson College of Veterinary Medicine, Oregon State University, Corvallis, OR., Morgun A; College of Pharmacy, Oregon State University, Corvallis, OR.
Jazyk:	angličtina
Zdroj:	The Journal of experimental medicine [J Exp Med] 2022 Jul 04; Vol. 219 (7). Date of Electronic Publication: 2022 Jun 03.
DOI:	10.1084/jem.20220017
Abstrakt:	Microbiota contribute to the induction of type 2 diabetes by high-fat/high-sugar (HFHS) diet, but which organs/pathways are impacted by microbiota remain unknown. Using multiorgan network and transkingdom analyses, we found that microbiota-dependent impairment of OXPHOS/mitochondria in white adipose tissue (WAT) plays a primary role in regulating systemic glucose metabolism. The follow-up analysis established that Mmp12+ macrophages link microbiota-dependent inflammation and OXPHOS damage in WAT. Moreover, the molecular signature of Mmp12+ macrophages in WAT was associated with insulin resistance in obese patients. Next, we tested the functional effects of MMP12 and found that Mmp12 genetic deficiency or MMP12 inhibition improved glucose metabolism in conventional, but not in germ-free mice. MMP12 treatment induced insulin resistance in adipocytes. TLR2-ligands present in Oscillibacter valericigenes bacteria, which are expanded by HFHS, induce Mmp12 in WAT macrophages in a MYD88-ATF3-dependent manner. Thus, HFHS induces Mmp12+ macrophages and MMP12, representing a microbiota-dependent bridge between inflammation and mitochondrial damage in WAT and causing insulin resistance. (© 2022 Li et al.)
Databáze:	MEDLINE
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