title: Increased apoptosis and browning of TAK1-deficient adipocytes protects against obesity.
abstract: Obesity is an increasing health problem worldwide, and nonsurgical strategies to treat obesity have remained rather inefficient. We here show that acute loss of TGF-β-activated kinase 1 (TAK1) in adipocytes results in an increased rate of apoptotic adipocyte death and increased numbers of M2 macrophages in white adipose tissue. Mice with adipocyte-specific TAK1 deficiency have reduced adipocyte numbers and are resistant to obesity induced by a high-fat diet or leptin deficiency. In addition, adipocyte-specific TAK1-deficient mice under a high-fat diet showed increased energy expenditure, which was accompanied by enhanced expression of the uncoupling protein UCP1. Interestingly, acute induction of adipocyte-specific TAK1 deficiency in mice already under a high-fat diet was able to stop further weight gain and improved glucose tolerance. Thus, loss of TAK1 in adipocytes reduces the total number of adipocytes, increases browning of white adipose tissue, and may be an attractive strategy to treat obesity, obesity-dependent diabetes, and other associated complications.
authors.affiliation: Department of Pharmacology and.
authors.forename: Antonia
authors.initials: A
authors.lastname: Sassmann-Schweda
authors.affiliation: Department of Pharmacology and.
authors.forename: Pratibha
authors.initials: P
authors.lastname: Singh
authors.affiliation: Department of Pharmacology and.
authors.forename: Cong
authors.initials: C
authors.lastname: Tang
authors.affiliation: Scientific Service Group Nuclear Magnetic Resonance Imaging, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Wietelmann
authors.affiliation: Department of Pharmacology and.|Medical Faculty, Goethe-University Frankfurt, Frankfurt, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Wettschureck
authors.affiliation: Department of Pharmacology and.|Medical Faculty, Goethe-University Frankfurt, Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Offermanns
mesh_terms: D017667:Adipocytes / Q000166:cytology; D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D059305:Diet, High-Fat; D020930:MAP Kinase Kinase Kinases / Q000172:deficiency* / Q000235:genetics; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics*; D000071256:Uncoupling Protein 1 / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D020930:MAP Kinase Kinase Kinases; D000071256:Uncoupling Protein 1; D000099151:MAP Kinase Kinase Kinase 7; C000604372:Ucp1 protein, mouse