Insulin Depletion Leads to Adipose-Specific Cell Death in Obese but not Lean Mice

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 95; no. 24; pp. 14168 - 14172
• Main Authors: Loftus, Thomas M., Kuhajda, Francis P., Lane, M. Daniel
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 24.11.1998; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences
• Subjects: 3T3 Cells; Adipocytes; Adipocytes - cytology; Adipocytes - physiology; Adipose Tissue - cytology; Adipose Tissue - pathology; Adipose tissues; Animals; Antibodies; Biological Sciences; Blood Glucose - metabolism; Cell Death; Cellular biology; DNA; Genetics; Glucose Tolerance Test; Hyperinsulinism; Insulin; Insulin - blood; Insulin - physiology; Insulin Antibodies - pharmacology; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Mutation; Obesity; Obesity - genetics; Obesity - pathology; Obesity - physiopathology; RNA; Rodents; Thinness
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.95.24.14168

Mutation of the obese gene produces obesity, hyperinsulinemia, and compensatory ``overexpression'' of the defective gene. As insulin activates obese gene expression, it seemed possible that hyperinsulinemia might be responsible for overexpression of the gene. To address this question we rapidly neutralized circulating insulin by injection of an insulin antibody. Unexpectedly, insulin depletion in obese (ob/ob or db/db) mice caused massive adipose RNA degradation confirmed by histological analysis to result from adipocyte cell death by a largely necrotic mechanism. This effect was not observed in lean littermates and was completely corrected by coadministration of insulin. Comparison of multiple tissues demonstrated that the effect was restricted to adipose tissue. Insulin depletion in obese mice by administration of streptozotocin also led to cell death, but this death was less extensive and appeared to be apoptotic in mechanism. Thus insulin may promote the survival side of the physiological balance between adipocyte survival and death.