Korean J Physiol Pharmacol.  2019 May;23(3):161-169. 10.4196/kjpp.2019.23.3.161.

Fumigaclavine C attenuates adipogenesis in 3T3-L1 adipocytes and ameliorates lipid accumulation in high-fat diet-induced obese mice

• Yu WG
• He Y
• Chen YF
• Gao XY
• Ning WE
• Liu CY
• Tang TF
• Liu Q
• Huang XC

• KMID: 2443604
• DOI: http://doi.org/10.4196/kjpp.2019.23.3.161

Abstract

Fumigaclavine C (FC), an active indole alkaloid, is obtained from endophytic Aspergillus terreus (strain No. FC118) by the root of Rhizophora stylosa (Rhizophoraceae). This study is designed to evaluate whether FC has anti-adipogenic effects in 3T3-L1 adipocytes and whether it ameliorates lipid accumulation in high-fat diet (HFD)-induced obese mice. FC notably increased the levels of glycerol in the culture supernatants and markedly reduced lipid accumulation in 3T3-L1 adipocytes. FC differentially inhibited the expressions of adipogenesis-related genes, including the peroxisome proliferator-activated receptor proteins, CCAAT/enhancer-binding proteins, and sterol regulatory element-binding proteins. FC markedly reduced the expressions of lipid synthesis-related genes, such as the fatty acid binding protein, lipoprotein lipase, and fatty acid synthase. Furthermore, FC significantly increased the expressions of lipolysis-related genes, such as the hormone-sensitive lipase, Aquaporin-7, and adipose triglyceride lipase. In HFD-induced obese mice, intraperitoneal injections of FC decreased both the body weight and visceral adipose tissue weight. FC administration significantly reduced lipid accumulation. Moreover, FC could dose-dependently and differentially regulate the expressions of lipid metabolism-related transcription factors. All these data indicated that FC exhibited anti-obesity effects through modulating adipogenesis and lipolysis.

Keyword

Adipogenesis; Anti-obesity; Fumigaclavine C; Lipolysis

MeSH Terms

Adipocytes*
Adipogenesis*
Animals
Aspergillus
Body Weight
Carrier Proteins
Diet, High-Fat
Glycerol
Injections, Intraperitoneal
Intra-Abdominal Fat
Lipase
Lipolysis
Lipoprotein Lipase
Mice
Mice, Obese*
Peroxisomes
Rhizophoraceae
Sterol Esterase
Transcription Factors
Carrier Proteins
Glycerol
Lipase
Lipoprotein Lipase
Sterol Esterase
Transcription Factors

Figure

• 

  Fig. 1 Effects of fumigaclavine C (FC) on adipogenesis in differentiated 3T3-L1 adipocytes. (A) The chemical structure of FC. (B) Effects of FC on 3T3-L1 adipocytes viability. (C) Effects of FC on lipid accumulation in differentiated 3T3-L1 adipocytes. Cells were treated with isopropanol and lipid accumulation was determined by the absorbance at optical density 490 nm. (D) Effects of FC on levels of glycerol in differentiated 3T3-L1 adipocytes. Simvastatin (Sim, 10 µM) acted as the positive control group. Each value represents as means ± standard error of the mean of triplicate experiments. *p < 0.05 and **p < 0.01 as compared with the control group.

• 

  Fig. 2 Fumigaclavine C (FC) differentially regulates the expressions of adipogenesis-related genes and proteins. Differentiated 3T3-L1 adipocytes were treated with FC or Simvastatin (Sim) for 24 h. These adipogenesis-related genes were evaluated via real-time polymerase chain reaction and Western blot technique. β-actin was used as an internal control. (A, B) Effects of FC on protein productions of adipogenesis-related genes in differentiated 3T3-L1 adipocytes. (C) Effects of FC on mRNA expressions of adipogenesis-related genes in differentiated 3T3-L1 adipocytes. Sim (10 µM) acted as the positive control group. Each value represents as means ± standard error of the mean of triplicate experiments. PPAR, peroxisome proliferator-activated receptors; C/EBP, CCAAT/enhancer-binding proteins; SREBP, sterol regulatory element-binding proteins. *p < 0.05 and **p < 0.01 as compared with the control group.

• 

  Fig. 3 Effects of fumigaclavine C (FC) on the expressions of lipid synthesis-related genes and proteins. Differentiated 3T3-L1 adipocytes were treated with FC or Simvastatin (Sim) for 24 h. These lipid synthesis-related genes were evaluated via real-time polymerase chain reaction and Western blot technique. β-actin was used as an internal control. (A, B) Effects of FC on protein productions of lipid synthesis-related genes in differentiated 3T3-L1 adipocytes. (C) Effects of FC on mRNA expressions of lipid synthesis-related genes in differentiated 3T3-L1 adipocytes. Sim (10 µM) acted as the positive control group. Each value represents as means ± standard error of the mean of triplicate experiments. aP2, fatty acid-binding protein; LPL, lipoprotein lipase; FAS, fatty acid synthase. *p < 0.05 and **p < 0.01 as compared with the control group.

• 

  Fig. 4 Effects of fumigaclavine C (FC) on the expressions of lipolysis-related genes and proteins. Differentiated 3T3-L1 adipocytes were treated with FC or Simvastatin (Sim) for 24 h. These lipolysis-related genes were evaluated via real-time polymerase chain reaction and Western blot technique. β-actin was used as an internal control. (A, B) Effects of FC on protein productions of lipolysis-related genes in differentiated 3T3-L1 adipocytes. (C) Effects of FC on mRNA expressions of lipolysis-related genes in differentiated 3T3-L1 adipocytes. Sim (10 µM) acted as the positive control group. Each value represents as means ± standard error of the mean of triplicate experiments. HSL, hormone-sensitive lipase; AQP-7, aquaporin-7; ATGL, adipose triglyceride lipase. *p < 0.05 and **p < 0.01 as compared with the control group.

• 

  Fig. 5 Effects of fumigaclavine C (FC) administration on the body weight, visceral adipocyte tissue weight, and plasma levels of in high-fat diet (HFD)-induced obese mice. Inhibitory effects of FC administration on the body weight (A) and visceral adipocyte tissue weight (B). Diagnostic kits were used to measure the plasma levels of triglyceride (TG) (C) and total cholesterol (TC) (D) in HFD-induced obese mice. Simvastatin (Sim) (20 mg/kg) acted as the positive control group. Each value represents as means ± standard error of the mean of 10 mice. #p < 0.01 as compared with the control group. *p < 0.05 and **p < 0.01 as compared with the HFD-induced group.

• 

  Fig. 6 Effects of fumigaclavine C (FC) administration on the lipid metabolism-related factors expressions in the visceral adipocyte tissue of high-fat diet (HFD)-induced obese mice. Real-time polymerase chain reaction (A) and Western blotting (B, C) were used to measure the expressions of PPAR-α, PPAR-β, PPAR-γ, C/EBP-α, C/EBP-β, SREBP-1c, aP2, LPL, FAS, HSL, AQP-7, and ATGL in the visceral adipocyte tissue. Simvastatin (Sim) (20 mg/kg) acted as the positive control group. Each value represents as means ± standard error of the mean of 10 mice. PPAR, peroxisome proliferator-activated receptors; C/EBP, CCAAT/enhancer-binding proteins; SREBP, sterol regulatory element-binding proteins; aP2, fatty acid-binding protein; LPL, lipoprotein lipase; FAS, fatty acid synthase; HSL, hormone-sensitive lipase; AQP-7, aquaporin-7; ATGL, adipose triglyceride lipase. #p < 0.01 as compared with the control group. *p < 0.05 and **p < 0.01 as compared with the HFD-induced group.

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