Figure 4

CREB3L3 fKO promotes weight gain by reducing energy expenditure and shifting brown fat lipid metabolism. (a) Energy expenditure and (b) respiratory exchange ratios (RER) of control and fKO mice fed high-fat diet (n = 6–8 mice per group). Energy expenditure was normalized to the animal’s lean mass. The curves for both measurements were analyzed using two-way ANOVA. P values for the column factor (genotype) for the energy expenditure and the RER were both < 0.0001. (c) Average daily consumption of high-fat diet while mice were in metabolic cages (n = 5–8 mice per group). (d) Activity measurements of control and fKO mice fed high-fat diet. Data presented as x- and y-axis beam breaks and total movement per day following acclimation period (n = 6–8 mice per group). (e) Representative images of H&E-stained brown adipose tissue sections following high-fat feeding. (f) Quantitative PCR for markers of fatty acid oxidation and lipogenesis in control and fKO brown adipose tissue following high-fat feeding (n = 5 mice per group). Expression was normalized to TBP and presented as fold change over controls. (g) Quantitative PCR for UCP1 and PGC1a in control and fKO inguinal adipose tissue in mice fed a chow diet (n = 5–6 mice per group). Target gene expression was normalized to TBP and presented as fold change over controls. (h) Quantitative PCR for markers of thermogenesis and adipocyte browning in iWAT from lean control and fKO mice following 10-day treatment with CL316,243 (n = 6 mice per group). Target gene expression was normalized to TBP and presented as fold change over the mean relative expression from the PBS-injected group for each respective genotype. (i) Body weight measurements for control and fKO mice consuming high-fat diet while housed at thermoneutrality for 10 wks (n = 7–9 mice per group). (j) Tissue weight measurements for control and fKO mice after consuming high-fat diet while housed at thermoneutrality for 10 wks (n = 7–9 mice per group). Data presented as mean ± SEM with sample sizes listed above. The difference in means was analyzed using Student’s t-test where *P < 0.05 and **P < 0.01, ***P < 0.001, and ****P < 0.0001.