The gene knockout of angiotensin II type 1a receptor improves high-fat diet-induced obesity in rat via promoting adipose lipolysis

Figures

• 

  Fig 1. AT1aR knockout improved insulin resistance and metabolic disorders in high-fat diet rats. A: Oral glucose tolerance test (OGTT) curve and area under the curve. B: Insulin tolerance test (ITT) curve and area under the curve. C: Fasting blood glucose (FBG). D: Blood pressure. E: Serum triglyceride (TG) levels. F: Serum total cholesterol (T-CHO). G: Serum free fatty acids (NEFAs). H: Serum glycerol. I: Serum low-density lipoprotein (LDL). J: Serum high-density lipoprotein (HDL). *p < 0.05 vs WT-ND rats; #p < 0.05 vs WT-HFD rats. Data were presented as Mean ± S.E.M. n = 6.

• 

  Fig 2. AT1aR knockout improved epididymal histomorphology induced by high fat diet. A, B: Body weight of rats was recorded weekly and body weight gain was calculated by weight increase in 12 weeks. C. Daily food intake of rats. D: Physical morphology of epididymal fat. E: Epididymal fat index (showed as epididymal fat weight/body weight). F: Adipocytes morphology was visualized by HE staining and adipocyte area were calculated by Image J. *p < 0.05 vs WT-ND rats; +p < 0.05 vs AT1aR-/—ND rats; Ψp < 0.05 vs WT-ND rats. Data were presented as Mean ± S.E.M. n = 6.

• 

  Fig 3. AT1aR knockout promoted adipose lipolysis. A, B: Gene expressions of key enzymes for lipid synthesis in adipose tissue, FAS (A) and ACC (B). C: Protein expressions of adipose lipolysis related enzymes, ATGL and HSL. D, E: Levels of NEFAs (D) and glycerol (E) in culture medium released by adipose tissue within 24 hours. *p < 0.05 vs WT-ND rats; +p < 0.05 vs AT1aR-/—ND rats. Data were presented as Mean ± S.E.M. n = 6.

• 

  Fig 4. AT1aR knockout elevated adipose energy expenditure and fatty acid oxidation. A-D: Gene expressions of PPARα (A), CD36 (B), CPT1 (C) and ACOX1 (D) in adipose tissue. E-H: Gene expressions of PPARδ (E), Dio2 (F), PGC-1α (G) and UCP1 (H) in adipose tissue. +p < 0.05 vs AT1aR-/—ND rats. Data were presented as Mean ± S.E.M. n = 6.

• 

  Fig 5. High fat diet activated Ang II-AT1R axis in rats. A. Protein expressions of kinases downstream of the Ang II-AT1R axis, p38 and ERK. B. Gene expression of Nox4 in adipose tissue. *p < 0.05 vs WT-ND rats. Data were presented as Mean ± S.E.M. n = 4.

• 

  Fig 6. AT1aR knockout activated cAMP/PKA pathway. A: Protein expressions of PKA, P-GSK-3β (ser9) and GSK-3β in adipose tissue. B: cAMP levels in adipose tissue. C: The proposed pathway for Ang II inhibiting adipose lipolysis. By binding to AT1R, Ang II activates inhibitory Gi which in turn reduces cAMP production. As a result, PKA activation is limited and HSL phosphorylation is decreased, leading to inhibitory of triglyceride hydrolysis. +p < 0.05 vs AT1aR-/—ND rats. Data were presented as Mean ± S.E.M. n = 6.