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

Author(s)

Castelli, Julia Z. ; Raposo, Helena F. ; Navarro, Claudia D. C. ; Lazaro, Carolina M. ; Sartori, Marina R. ; Dalla Costa, Ana Paula ; Nogueira, Pedro A. S. ; Velloso, Licio A. ; Vercesi, Anibal E. ; Oliveira, Helena C. F.

• Document type: Journal article
• Source: FASEB JOURNAL; v. 39, n. 3, p. 13-pg., 2025-02-15.

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 degrees C). The aim of this study is to evaluate how CETP expression affects 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 degrees C. The body oxygen consumption in response to an isoproterenol challenge was 21% higher at 22 degrees 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 degrees 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 degrees 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. (AU)

• FAPESP's process: 19/13862-7 - CETP influence on endothelial function and myocardial infarction: possible relation with mitochondrial function
• Grantee: Carolina Martins Lazaro
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 23/02270-7 - Linking defects in DNA repair to activation of the inflammatory response via cGAS-STING and defects in mitophagy in mononuclear cells from humans with cognitive decline
• Grantee: Claudia Daniele Carvalho Navarro
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 19/02340-0 - The impact of cholesteryl ester transfer protein (CETP) expression on adiposity in thermoneutral condition and obesogenic diet: focus on white adipose tissue
• Grantee: Júlia Zago Castelli
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center
• Grantee: Licio Augusto Velloso
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC