Fabp4-Cre-mediated Sirt6 deletion impairs adipose tissue function and metabolic homeostasis in mice

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   Figure 1

   SIRT6 is decreased in white adipose tissues (WAT) of high-fat diet (HFD)-fed mice. (A) and (B) Western blot (A) and densitometric analysis (B) of SIRT6 in epididymal fat pads of male mice fed with 60% HFD for 5 months (n = 6 per group). Data are presented as mean ± s.e.m. *P < 0.05.
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   Figure 2

   Fabp4-Cre-mediated Sirt6 deletion in mice leads to obesity. (A) and (B) Western blot (A) and real-time PCR (B) analysis of SIRT6 protein and Sirt6 mRNA in WAT and BAT of 3-month-old control and Sirt6^f/f:Fabp4-Cre (FKO) mice (n = 3 per genotype). (C) and (D) Body weight (C) and epididymal fat pad weight (D) of 3-month-old male control and FKO mice (n = 6–8 per genotype). (E) H&E staining of WAT and BAT from 6-month-old control and FKO mice. (F) Relative mRNA levels of thermogenic genes in BAT of 3-month-old control and FKO mice (n = 3 per genotype). (G) Plasma triglyceride and total cholesterol levels of 3-month-old male control and FKO mice (n = 6–8 per genotype). Data are presented as mean ± s.e.m. *P < 0.05. A full colour version of this figure is available at http://dx.doi.org/10.1530/JOE-17-0033.
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   Figure 3

   Sirt6-FKO mice exhibit glucose intolerance and insulin resistance. (A) and (B) Glucose tolerance test (GTT, 2 g/kg) (A) and insulin tolerance test (ITT, 0.5 U/kg) (B) in control and FKO mice at 3–4 months of age (n = 7–9 per genotype). (C) and (D) Western blot for the phosphorylated and total AKT proteins in WAT (C) and quantification by densitometry of phosphorylated AKT (p-AKT473) normalized to total AKT (D) for control and FKO mice at 3 months of age (n = 5 per genotype). (E) and (F) Mice were injected with 0.5 U/kg insulin for 3 min. Western blot (E) and quantification by densitometry of phosphorylated AKT (p-AKT473) normalized to total AKT (F) in WAT of control and FKO mice at 3 months of age (n = 5 per genotype). (G) Relative mRNA levels of leptin and adiponectin in WAT samples of 2-month-old male control and FKO mice (n = 4 per genotype). (H) Western blot analysis of adiponectin (Adipoq) protein level in 3-month-old control and FKO mice (n = 3 per genotype). Data are presented as mean ± s.e.m. *P < 0.05.
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   Figure 4

   Sirt6-FKO mice have increased adipose tissue inflammation. (A) and (B) Relative mRNA levels of inflammation-related genes in WAT samples (A) and BAT samples (B) of 6-month-old male control and FKO mice (n = 4–5 per genotype). Data are presented as mean ± s.e.m. *P < 0.05.
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   Figure 5

   Deletion of Sirt6 in mature adipocytes using Adipoq-Cre. (A) and (B) Western blot (A) and real-time PCR (B) analysis of SIRT6 protein and Sirt6 mRNA in WAT and BAT of 2-month-old control and Sirt6^f/f:Adipoq-Cre (AKO) mice (n = 3 per genotype). (C) Body weight of control and AKO male mice with different ages (n = 6–8 per genotype). Data are presented as mean ± s.e.m. *P < 0.05.
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   Figure 6

   Challenge of Sirt6-AKO mice with a high-fat diet. Control and AKO male mice were fed with HFD (60% calorie from fat) for 3 months. (A) Body weight of control and AKO mice before and after the HFD feeding (n = 7–8 per genotype). (B) and (C) Glucose tolerance test (GTT, 1.5 g/kg) (B) and insulin tolerance test (ITT, 0.75 U/kg) (C) in control and AKO mice fed with HFD for 3 months (n = 7–8 per genotype). (D) Relative mRNA levels of TNFα and IL-6 in WAT of HFD-fed control and AKO mice (n = 4–5 per genotype). Data are presented as mean ± s.e.m. *P < 0.05.

• © 2017 Society for Endocrinology