title: Ablation of LGR4 promotes energy expenditure by driving white-to-brown fat switch.
abstract: Obesity occurs when excess energy accumulates in white adipose tissue (WAT), whereas brown adipose tissue (BAT), specialized for energy expenditure through thermogenesis, potently counteracts obesity. Factors that induce brown adipocyte commitment and energy expenditure would be a promising defence against adiposity. Here, we show that Lgr4 homozygous mutant (Lgr4(m/m)) mice show reduced adiposity and resist dietary and leptin mutant-induced obesity with improved glucose metabolism. Lgr4(m/m) mice show a striking increase in energy expenditure, and exhibit brown-like adipocytes in WAT depots with higher expression of BAT and beige cell markers. Furthermore, Lgr4 ablation potentiates brown adipocyte differentiation from the stromal vascular fraction of epididymal WAT, partially through retinoblastoma 1 gene (Rb1) reduction. A functional low-frequency human LGR4 variant (A750T) has been associated with body mass index in a Chinese obese-versus-control study. Our results identify an important role for LGR4 in energy balance and body weight control through regulating the white-to-brown fat transition.
authors.affiliation: 1] Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Shanghai Key Laboratory for Endocrine Tumors and E-Institute of Shanghai Universities, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin 2nd Road, Shanghai 200025, China [2].
authors.forename: Jiqiu
authors.initials: J
authors.lastname: Wang
authors.forename: Ruixin
authors.initials: R
authors.lastname: Liu
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Hong
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Li
authors.forename: Maopei
authors.initials: M
authors.lastname: Chen
authors.forename: Yingying
authors.initials: Y
authors.lastname: Ke
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Zhang
authors.forename: Qinyun
authors.initials: Q
authors.lastname: Ma
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Juan
authors.initials: J
authors.lastname: Shi
authors.forename: Bin
authors.initials: B
authors.lastname: Cui
authors.forename: Weiqiong
authors.initials: W
authors.lastname: Gu
authors.forename: Yifei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Weiqing
authors.initials: W
authors.lastname: Wang
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Xia
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
mesh_terms: D017667:Adipocytes / Q000502:physiology; D050156:Adipogenesis; D002001:Adipose Tissue, Brown / Q000378:metabolism* / Q000473:pathology; D052436:Adipose Tissue, White / Q000378:metabolism* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D016022:Case-Control Studies; D004734:Energy Metabolism; D005260:Female; D056726:Genetic Association Studies; D057809:HEK293 Cells; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D008820:Mice, Obese; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: C411562:LGR4 protein, human; D043562:Receptors, G-Protein-Coupled