Transplantation of adipose tissue lacking leptin is unable to reverse the metabolic abnormalities associated with lipoatrophy.
Severe adipose tissue deficiency (lipoatrophy) causes insulin-resistant diabetes, elevated serum triglyceride and fatty acid levels, and massive triglyceride deposition in the liver. In lipoatrophic A-ZIP/F-1 mice, transplantation of normal adipose tissue greatly improved these parameters, whereas 1 week of leptin infusion had more modest effects. In contrast, leptin infusion was strikingly more effective in the aP2-n sterol response element binding protein 1 lipoatrophic mouse. Here we show that a longer duration of leptin infusion further improves the metabolic status of the A-ZIP/F-1 mice and that genetic background does not make a major contribution to the effect of leptin on glucose and insulin levels. Adipose transplantation using leptin-deficient ob/ob fat had no effect on the phenotype of the A-ZIP/F-1 mice. Moreover, the presence of ob/ob adipose tissue did not enhance the effects of leptin infusion. Serum adiponectin levels were 2% of control levels in the A-ZIP/F-1 mouse and increased only twofold with adipose transplantation and not at all after leptin infusion, suggesting that adiponectin deficiency is not a major contributor to the diabetic phenotype. Taken together, these results suggest that sequestration of triglycerides into fat may not be enough to restore a nondiabetic phenotype and that leptin deficiency plays a major role in causing the metabolic complications of lipoatrophy.
Colombo
Carlo
C
Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Cutson
Jaime J
JJ
Yamauchi
Toshimasa
T
Vinson
Charles
C
Kadowaki
Takashi
T
Gavrilova
Oksana
O
Reitman
Marc L
ML
D052242:Adiponectin; D000273:Adipose Tissue / Q000378:metabolism* / Q000637:transplantation*; D000818:Animals; D003923:Diabetes Mellitus, Lipoatrophic / Q000235:genetics / Q000378:metabolism* / Q000601:surgery*; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin / Q000172:deficiency* / Q000627:therapeutic use; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D011506:Proteins / Q000502:physiology; D017211:Treatment Failure
D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D011506:Proteins