title: Obesity-associated improvements in metabolic profile through expansion of adipose tissue.
abstract: Excess caloric intake can lead to insulin resistance. The underlying reasons are complex but likely related to ectopic lipid deposition in nonadipose tissue. We hypothesized that the inability to appropriately expand subcutaneous adipose tissue may be an underlying reason for insulin resistance and beta cell failure. Mice lacking leptin while overexpressing adiponectin showed normalized glucose and insulin levels and dramatically improved glucose as well as positively affected serum triglyceride levels. Therefore, modestly increasing the levels of circulating full-length adiponectin completely rescued the diabetic phenotype in ob/ob mice. They displayed increased expression of PPARgamma target genes and a reduction in macrophage infiltration in adipose tissue and systemic inflammation. As a result, the transgenic mice were morbidly obese, with significantly higher levels of adipose tissue than their ob/ob littermates, leading to an interesting dichotomy of increased fat mass associated with improvement in insulin sensitivity. Based on these data, we propose that adiponectin acts as a peripheral "starvation" signal promoting the storage of triglycerides preferentially in adipose tissue. As a consequence, reduced triglyceride levels in the liver and muscle convey improved systemic insulin sensitivity. These mice therefore represent what we believe is a novel model of morbid obesity associated with an improved metabolic profile.
authors: Department of Cell Biology, Albert Einstein College of Medicine, New York, New York, USA.
authors: Ja-Young
authors: JY
authors: Kim
authors: Esther
authors: E
authors: van de Wall
authors: Mathieu
authors: M
authors: Laplante
authors: Anthony
authors: A
authors: Azzara
authors: Maria E
authors: ME
authors: Trujillo
authors: Susanna M
authors: SM
authors: Hofmann
authors: Todd
authors: T
authors: Schraw
authors: Jorge L
authors: JL
authors: Durand
authors: Hua
authors: H
authors: Li
authors: Guangyu
authors: G
authors: Li
authors: Linda A
authors: LA
authors: Jelicks
authors: Mark F
authors: MF
authors: Mehler
authors: David Y
authors: DY
authors: Hui
authors: Yves
authors: Y
authors: Deshaies
authors: Gerald I
authors: GI
authors: Shulman
authors: Gary J
authors: GJ
authors: Schwartz
authors: Philipp E
authors: PE
authors: Scherer
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000273:Adipose Tissue / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D000821:Animal Feed; D000818:Animals; D004075:Diglycerides / Q000378:metabolism; D005223:Fats / Q000494:pharmacology; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D020738:Leptin / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008264:Macrophages; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D009929:Organ Size; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D010641:Phenotype; D014280:Triglycerides / Q000378:metabolism
chemical_list: D052242:Adiponectin; D004075:Diglycerides; D005223:Fats; D007328:Insulin; D020738:Leptin; D008074:Lipoproteins; D047495:PPAR gamma; D014280:Triglycerides
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