title: Adipose tissue supports normalization of macrophage and liver lipid handling in obesity reversal.
abstract: Adipose tissue inflammation and dysfunction are considered central in the pathogenesis of obesity-related dysmetabolism, but their role in the rapid metabolic recovery upon obesity reversal is less well defined. We hypothesized that changes in adipose tissue endocrine and paracrine mechanisms may support the rapid improvement of obesity-induced impairment in cellular lipid handling. C57Bl-6J mice were fedad libitumeither normal chow (NC) or high-fat diet (HFF) for 10 weeks. A dietary obesity reversal group was fed HFF for 8 weeks and then switched to NC for 2 weeks (HFF→NC). Whole-body glucose homeostasis rapidly nearly normalized in the HFF→NC mice (fasting glucose and insulin fully normalized, glucose and insulin tolerance tests reversed 82% to the NC group levels). During 2 weeks of the dietary reversal, the liver was significantly cleared from ectopic fat, and functionally, glucose production from pyruvate, alanine or fructose was normalized. In contrast, adipose tissue inflammation (macrophage infiltration and polarization) largely remained as in HFF, though obesity-induced adipose tissue macrophage lipid accumulation decreased by ~50%, and adipose tissue MAP kinase hyperactivation was reversed.Ex vivo, mild changes in adipose tissue adipocytokine secretion profile were noted. These corresponded to partial or full reversal of the excess cellular lipid droplet accumulation induced by HFF adipose tissue conditioned media in hepatoma or macrophage cells, respectively. We propose that early after initiating reversal of nutritional obesity, rapid metabolic normalization largely precedes resolution of adipose tissue inflammation. Nevertheless, we demonstrate a hitherto unrecognized contribution of adipose tissue to the rapid improvement in lipid handling by the liver and by macrophages.
authors.affiliation: The Department of Clinical Biochemistry and PharmacologyFaculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.|The National Institute of Biotechnology in the Negev (NIBN)Ben-Gurion University, Beer-Sheva, Israel.
authors.forename: Maayan
authors.initials: M
authors.lastname: Vatarescu
authors.affiliation: The Department of Clinical Biochemistry and PharmacologyFaculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.|The National Institute of Biotechnology in the Negev (NIBN)Ben-Gurion University, Beer-Sheva, Israel.
authors.forename: Sapir
authors.initials: S
authors.lastname: Bechor
authors.affiliation: The Department of Clinical Biochemistry and PharmacologyFaculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.|The National Institute of Biotechnology in the Negev (NIBN)Ben-Gurion University, Beer-Sheva, Israel.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Haim
authors.affiliation: The Department of Clinical Biochemistry and PharmacologyFaculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.|The National Institute of Biotechnology in the Negev (NIBN)Ben-Gurion University, Beer-Sheva, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Pecht
authors.affiliation: The Department of Clinical Biochemistry and PharmacologyFaculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Tanya
authors.initials: T
authors.lastname: Tarnovscki
authors.affiliation: The Department of Clinical Biochemistry and PharmacologyFaculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Noa
authors.initials: N
authors.lastname: Slutsky
authors.affiliation: The Department of Clinical Biochemistry and PharmacologyFaculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Ori
authors.initials: O
authors.lastname: Nov
authors.affiliation: The Department of Clinical Biochemistry and PharmacologyFaculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Hagit
authors.initials: H
authors.lastname: Shapiro
authors.affiliation: The Shraga Segal Department of MicrobiologyImmunology and Genetics, Ben-Gurion University, Beer-Sheva, Israel.
authors.forename: Avishai
authors.initials: A
authors.lastname: Shemesh
authors.affiliation: The Shraga Segal Department of MicrobiologyImmunology and Genetics, Ben-Gurion University, Beer-Sheva, Israel.
authors.forename: Angel
authors.initials: A
authors.lastname: Porgador
authors.affiliation: The Department of Clinical Biochemistry and PharmacologyFaculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Nava
authors.initials: N
authors.lastname: Bashan
authors.affiliation: The Department of Clinical Biochemistry and PharmacologyFaculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel rudich@bgu.ac.il.|The National Institute of Biotechnology in the Negev (NIBN)Ben-Gurion University, Beer-Sheva, Israel.
authors.forename: Assaf
authors.initials: A
authors.lastname: Rudich
mesh_terms: D000273:Adipose Tissue / Q000502:physiology*; D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology; D050356:Lipid Metabolism / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism*; D015431:Weight Loss
keywords: adipose tissue inflammation; adipose tissue macrophages; glucose production; insulin resistance; obesity reversal