CETP expression in females increases body metabolism under both cold exposure and thermoneutrality contributing to a leaner phenotype

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 non-transgenic (NTg) littermates under standard housing temperature (22{degrees}C). The aim of this study is to evaluate how CETP expression affect body temperature, composition and metabolism during cold exposure (4{degrees}C) and thermoneutrality (30{degrees}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{o}C. The body oxygen consumption in response to an isoproterenol challenge was 21% higher at 22{o}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{o}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{o}C. In this thermoneutrality 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. NEW & NOTEWORTHYWe demonstrate here that CETP expression in females increases body metabolism under cold (4{o}C) and thermoneutrality (30{o}C). Since this has also been shown at 22{o}C, it seems a constitutive feature of CETP expression. Brown adipose tissue and red fiber muscle contribute to the overall high metabolism and leaner phenotype of CETP mice. Elevated mitochondrial respiration rates were demonstrated in these tissues. Thus, CETP is a new relevant variable in the context of obesity and metabolic disorders. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/623058v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@19ed73org.highwire.dtl.DTLVardef@3458acorg.highwire.dtl.DTLVardef@a9896forg.highwire.dtl.DTLVardef@7e1138_HPS_FORMAT_FIGEXP M_FIG C_FIG