title: Kupffer cell depletion prevents but has no therapeutic effect on metabolic and inflammatory changes induced by a high-fat diet.
abstract: We aimed to evaluate activation of macrophages in insulin-sensitive tissues (liver, adipose tissue, and muscles) under high-fat diet (HFD) and elucidate the role of Kupffer cells (KC) in HFD-induced insulin resistance. Tissue macrophage populations, insulin signaling, and sensitivity were evaluated in mice fed a HFD for 4 or 16 wk. Selective KC depletion was obtained by intravenous injections of liposome-encapsulated clodronate. Mice fed a HFD for 4 to 16 wk have hepatic and peripheral insulin resistance together with macrophage recruitment in the adipose tissue but not in the liver. Depletion of KC for the last 10 d of the 16 wk experiment fails to improve insulin sensitivity compared to PBS-treated animals. In contrast, preventive KC depletion prior to and during the 4 wk HFD attenuates the development of obesity, adiposity, adipose tissue inflammation (P<0.01 vs. PBS group), and insulin resistance (P<0.01). Interestingly, in mice fed a normal diet, prolonged KC depletion ameliorates insulin sensitivity and decreases adiposity without altering physiological body weight gain or food intake. Preventive and prolonged KC depletion ameliorates insulin sensitivity and prevents adipose tissue inflammation, suggesting a communication between the liver and the adipose tissue in the development of HFD-induced metabolic alterations.
authors.affiliation: Laboratoire d'Hépato-Gastro-Entérologie, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, UCL/GAEN 5379, Ave. E Mounier 53, 1200 Brussels, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lanthier
authors.forename: Olivier
authors.initials: O
authors.lastname: Molendi-Coste
authors.forename: Patrice D
authors.initials: PD
authors.lastname: Cani
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Yves
authors.initials: Y
authors.lastname: Horsmans
authors.forename: Isabelle A
authors.initials: IA
authors.lastname: Leclercq
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050154:Adiposity; D000818:Animals; D004002:Clodronic Acid / Q000494:pharmacology; D059305:Diet, High-Fat / Q000009:adverse effects*; D005234:Fatty Liver / Q000517:prevention & control; D007249:Inflammation / Q000517:prevention & control; D007333:Insulin Resistance / Q000502:physiology*; D007728:Kupffer Cells / Q000187:drug effects / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000517:prevention & control
chemical_list: D004002:Clodronic Acid