Objective: CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP)‐10/growth arrest and DNA damage 153 is a dominant‐negative member of the C/EBP transcription family and inhibits adipogenesis in vitro. The study was undertaken to determine the role of CHOP in obesity in vivo.

Research Methods and Procedures: Changes in daily food consumption and body weight were measured. The weight of white and brown adipose tissue was compared between Chop(+/+) and (−/−) mice fed normal chow or a high‐fat diet. Glucose and insulin tolerance tests were done, and serum adipocytokine was measured to determine their metabolic state. Fat cell size of subcutaneous and mesenteric adipose tissue was microscopically observed. C/EBP expression in white adipose tissue was examined by Western blot.

Results: Female Chop(−/−) mice had significantly greater body weight and adiposity than Chop(+/+) mice, although daily food intake and rectal temperature did not differ. In comparison with Chop(+/+) mice, glucose tolerance and insulin sensitivity did not differ in female Chop(−/−) mice, but levels of plasma leptin and adiponectin were higher. High‐fat diet feeding resulted in obesity in female Chop(+/−) and (−/−) mice, although caloric intake did not differ from that of Chop(+/+) mice. Fat cell area was larger in mesenteric fat but not in subcutaneous fat in Chop(−/−) mice fed a high‐fat diet. C/EBPβ and the 30‐kDa form of C/EBPα expressions were increased in parametrial fat of Chop(−/−) mice, but the 42‐kDa form of C/EBPα expression was lower than in Chop(+/+) mice.

Discussion: CHOP deficiency causes obesity in female animals without severe metabolic disorders, and C/EBP's expression may be considered to participate in the process.