title: Clodronate liposomes improve metabolic profile and reduce visceral adipose macrophage content in diet-induced obese mice.
abstract: BACKGROUND
  Obesity-related adipose inflammation has been thought to be a causal factor for the development of insulin resistance and type 2 diabetes. Infiltrated macrophages in adipose tissue of obese animals and humans are an important source for inflammatory cytokines. Clodronate liposomes can ablate macrophages by inducing apoptosis. In this study, we aim to determine whether peritoneal injection of clodronate liposomes has any beneficial effect on systemic glucose homeostasis/insulin sensitivity and whether macrophage content in visceral adipose tissue will be reduced in diet-induced obese (DIO) mice.
  
  
  RESULTS
  Clodronate liposomes were used to deplete macrophages in lean and DIO mice. Macrophage content in visceral adipose tissue, metabolic parameters, glucose and insulin tolerance, adipose and liver histology, adipokine and cytokine production were examined. Hyperinsulinemic-euglycemic clamp study was also performed to assess systemic insulin sensitivity. Peritoneal injection of clodronate liposomes significantly reduced blood glucose and insulin levels in DIO mice. Systemic glucose tolerance and insulin sensitivity were mildly improved in both lean and DIO mice treated with clodronate liposomes by intraperitoneal (i.p.) injection. Hepatosteatosis was dramatically alleviated and suppression of hepatic glucose output was markedly increased in DIO mice treated with clodronate liposomes. Macrophage content in visceral adipose tissue of DIO mice was effectively decreased without affecting subcutaneous adipose tissue. Interestingly, levels of insulin sensitizing hormone adiponectin, including the high molecular weight form, were significantly elevated in circulation.
  
  
  CONCLUSIONS
  Intraperitoneal injection of clodronate liposomes reduces visceral adipose tissue macrophages, improves systemic glucose homeostasis and insulin sensitivity in DIO mice, which can be partially attributable to increased adiponectin levels.
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Feng
authors.forename: Ping
authors.initials: P
authors.lastname: Jiao
authors.forename: Yaohui
authors.initials: Y
authors.lastname: Nie
authors.forename: Thomas
authors.initials: T
authors.lastname: Kim
authors.forename: Dale
authors.initials: D
authors.lastname: Jun
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Zaiqing
authors.initials: Z
authors.lastname: Yang
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xu
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D054392:Adipokines / Q000097:blood; D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D004002:Clodronic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D018920:Coculture Techniques; D004032:Diet; D005234:Fatty Liver / Q000188:drug therapy / Q000473:pathology; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D008081:Liposomes / Q000737:chemistry*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D055442:Metabolome / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009929:Organ Size / Q000187:drug effects; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014280:Triglycerides / Q000378:metabolism; D014781:Viscera / Q000473:pathology*
chemical_list: D054392:Adipokines; D001786:Blood Glucose; D007328:Insulin; D008081:Liposomes; D014280:Triglycerides; D004002:Clodronic Acid