Mechanisms
CETP expression raises body metabolism and leanness in female mice during both cold exposure and thermoneutrality (FASEB J 2025)
Original title: CETP expression in females increases body metabolism under both cold exposure and thermoneutrality contributing to a leaner phenotype
Building on earlier findings that CETP-expressing female mice are leaner than non-transgenic littermates at standard housing temperature, researchers tested how CETP expression affects body temperature, composition, and metabolism during cold exposure (4 degrees C) and thermoneutrality (30 degrees C). During cold exposure, CETP mice maintained similar rectal temperature and body weight to non-transgenic mice, but their oxygen consumption in response to an isoproterenol challenge was 21 percent higher at 22 degrees C and 41 percent higher after seven days of cold, alongside reduced brown fat lipid content. At thermoneutrality, when brown fat activity is suppressed, CETP mice instead showed higher body temperature, increased food intake and energy expenditure, more lean mass, less fat mass, and increased mitochondrial respiration in soleus muscle. The findings indicate CETP expression raises metabolic rate through brown fat activity in the cold and through muscle metabolism at thermoneutrality.
Original abstract
Susceptibility to obesity differs depending on the genetic background and housing temperatures. We have recently reported that CETP expressing female mice are leaner due to increased lipolysis, brown adipose tissue (BAT) activity, and body energy expenditure compared to nontransgenic (NTg) littermates under standard housing temperature (22°C). The aim of this study is to evaluate how CETP expression affects body temperature, composition, and metabolism during cold exposure (4°C) and thermoneutrality (30°C). When submitted to cold, CETP mice maintained rectal temperature, body weight, and food intake similarly to NTg mice along acute or chronic exposure to 4°C. The body oxygen consumption in response to an isoproterenol challenge was 21% higher at 22°C, and 41% higher after 7 days of cold exposure in CETP than in NTg mice. In addition, BAT biopsies from CETP mice showed reduced lipid content and increased basal oxygen consumption rates. Under thermoneutrality (30°C), when BAT activity is inhibited, CETP mice showed higher rectal and tail temperatures, increased food intake, and increased energy expenditure. Lean mass was elevated and fat mass reduced in CETP mice kept at 30°C. In this thermoneutral condition, soleus muscle, but not gastrocnemius or liver of CETP mice, showed increased mitochondrial respiration rates. These data indicate that CETP expression confers a greater capacity of elevating body metabolic rates at both cold exposure, through BAT activity, and at thermoneutrality, through increased muscle metabolism. Thus, the CETP expression levels in females should be considered as a new influence in the contexts of obesity and metabolic disorders propensity.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.