Limits...
Sudachitin, a polymethoxylated flavone, improves glucose and lipid metabolism by increasing mitochondrial biogenesis in skeletal muscle.

Tsutsumi R, Yoshida T, Nii Y, Okahisa N, Iwata S, Tsukayama M, Hashimoto R, Taniguchi Y, Sakaue H, Hosaka T, Shuto E, Sakai T - Nutr Metab (Lond) (2014)

Bottom Line: Flavonoids are effective antioxidants that protect against these chronic diseases.Sudachitin improved dyslipidemia, as evidenced by reduction in triglyceride and free fatty acid levels, and improved glucose tolerance and insulin resistance.The in vitro assay results suggest that sudachitin increased Sirt1 and PGC-1α expression in the skeletal muscle.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Public Health and Applied and Nutrition, Institute of Health Bioscience, University of Tokushima, 3-18-15 Kuramoto, Tokushima 770-8503, Japan.

ABSTRACT

Background: Obesity is a major risk factor for insulin resistance, type 2 diabetes, and stroke. Flavonoids are effective antioxidants that protect against these chronic diseases. In this study, we evaluated the effects of sudachitin, a polymethoxylated flavonoid found in the skin of the Citrus sudachi fruit, on glucose, lipid, and energy metabolism in mice with high-fat diet-induced obesity and db/db diabetic mice. In our current study, we show that sudachitin improves metabolism and stimulates mitochondrial biogenesis, thereby increasing energy expenditure and reducing weight gain.

Methods: C57BL/6 J mice fed a high-fat diet (40% fat) and db/db mice fed a normal diet were treated orally with 5 mg/kg sudachitin or vehicle for 12 weeks. Following treatment, oxygen expenditure was assessed using indirect calorimetry, while glucose tolerance, insulin sensitivity, and indices of dyslipidemia were assessed by serum biochemistry. Quantitative polymerase chain reaction was used to determine the effect of sudachitin on the transcription of key metabolism-regulating genes in the skeletal muscle, liver, and white and brown adipose tissues. Primary myocytes were also prepared to examine the signaling mechanisms targeted by sudachitin in vitro.

Results: Sudachitin improved dyslipidemia, as evidenced by reduction in triglyceride and free fatty acid levels, and improved glucose tolerance and insulin resistance. It also enhanced energy expenditure and fatty acid β-oxidation by increasing mitochondrial biogenesis and function. The in vitro assay results suggest that sudachitin increased Sirt1 and PGC-1α expression in the skeletal muscle.

Conclusions: Sudachitin may improve dyslipidemia and metabolic syndrome by improving energy metabolism. Furthermore, it also induces mitochondrial biogenesis to protect against metabolic disorders.

No MeSH data available.


Related in: MedlinePlus

Sudachitin reduces serum triglyceride and non-esterified fatty acid. Serum triglyceride (A), non-esterified fatty acid (B), and total cholesterol (C levels were evaluated at the end of the 12-week treatment. Values are means ± standard deviation (A-C). *P < 0.05 sudachitin administration vs. control treatment, # P < 0.05 high-fat diet-fed vs control diet-fed animals. Cont + Veh: vehicle-treated, control diet group (closed squares in panel A); Cont + Sud: sudachitin-treated, control diet group (open squares); HFD + Veh: vehicle-treated, high-fat diet group (closed circles); HFD + Sud: sudachitin-treated, high-fat diet group (open circles); NEFA: non-esterified fatty acid; T-CHO: total cholesterol.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4128574&req=5

Figure 3: Sudachitin reduces serum triglyceride and non-esterified fatty acid. Serum triglyceride (A), non-esterified fatty acid (B), and total cholesterol (C levels were evaluated at the end of the 12-week treatment. Values are means ± standard deviation (A-C). *P < 0.05 sudachitin administration vs. control treatment, # P < 0.05 high-fat diet-fed vs control diet-fed animals. Cont + Veh: vehicle-treated, control diet group (closed squares in panel A); Cont + Sud: sudachitin-treated, control diet group (open squares); HFD + Veh: vehicle-treated, high-fat diet group (closed circles); HFD + Sud: sudachitin-treated, high-fat diet group (open circles); NEFA: non-esterified fatty acid; T-CHO: total cholesterol.

Mentions: As shown in Figure 1A and B, treatment with 5 mg/kg body weight sudachitin reduced the weight gain in mice fed a high-fat diet, without affecting the food intake. By contrast, treatment with sudachitin did not affect the body weight in mice fed a low-fat control diet. Treatment of mice fed a high-fat diet with 2 mg/kg sudachitin did not affect the body weight of the animals (data not shown). The magnitude of weight reduction was similar between 5 and 10 mg/kg doses of sudachitin (data not shown), which prompted us to use the 5 mg/kg dose for subsequent investigations.A high-fat diet resulted in significantly elevated total body adipose tissue, increased subcutaneous fat deposits and elevated visceral fat (enlarged epididymal fat pads) which were ameliorated by 5 mg/kg sudachitin administration (Figure 2A–C). However, there were no differences in BAT or muscle weight per body weight among the four groups (data not shown). Sudachitin treatment also significantly reduced adipocyte size in high-fat diet-fed mice, as compared to the vehicle-treated mice fed high-fat diet (Figure 2D and E). Since these changes were independent of food intake and muscle mass, the results suggest that sudachitin improves energy metabolism.We next examined the effects of sudachitin on metabolic parameters. As expected, a high-fat diet significantly increased serum triglyceride and NEFA levels by 1.5- and 1.3-fold, respectively, compared with the control diet (Figure 3A and B). Administration of 5 mg/kg sudachitin prevented these increases in triglyceride and NEFA levels. Total cholesterol levels were not significantly different among any of the studied groups (Figure 3C).


Sudachitin, a polymethoxylated flavone, improves glucose and lipid metabolism by increasing mitochondrial biogenesis in skeletal muscle.

Tsutsumi R, Yoshida T, Nii Y, Okahisa N, Iwata S, Tsukayama M, Hashimoto R, Taniguchi Y, Sakaue H, Hosaka T, Shuto E, Sakai T - Nutr Metab (Lond) (2014)

Sudachitin reduces serum triglyceride and non-esterified fatty acid. Serum triglyceride (A), non-esterified fatty acid (B), and total cholesterol (C levels were evaluated at the end of the 12-week treatment. Values are means ± standard deviation (A-C). *P < 0.05 sudachitin administration vs. control treatment, # P < 0.05 high-fat diet-fed vs control diet-fed animals. Cont + Veh: vehicle-treated, control diet group (closed squares in panel A); Cont + Sud: sudachitin-treated, control diet group (open squares); HFD + Veh: vehicle-treated, high-fat diet group (closed circles); HFD + Sud: sudachitin-treated, high-fat diet group (open circles); NEFA: non-esterified fatty acid; T-CHO: total cholesterol.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4128574&req=5

Figure 3: Sudachitin reduces serum triglyceride and non-esterified fatty acid. Serum triglyceride (A), non-esterified fatty acid (B), and total cholesterol (C levels were evaluated at the end of the 12-week treatment. Values are means ± standard deviation (A-C). *P < 0.05 sudachitin administration vs. control treatment, # P < 0.05 high-fat diet-fed vs control diet-fed animals. Cont + Veh: vehicle-treated, control diet group (closed squares in panel A); Cont + Sud: sudachitin-treated, control diet group (open squares); HFD + Veh: vehicle-treated, high-fat diet group (closed circles); HFD + Sud: sudachitin-treated, high-fat diet group (open circles); NEFA: non-esterified fatty acid; T-CHO: total cholesterol.
Mentions: As shown in Figure 1A and B, treatment with 5 mg/kg body weight sudachitin reduced the weight gain in mice fed a high-fat diet, without affecting the food intake. By contrast, treatment with sudachitin did not affect the body weight in mice fed a low-fat control diet. Treatment of mice fed a high-fat diet with 2 mg/kg sudachitin did not affect the body weight of the animals (data not shown). The magnitude of weight reduction was similar between 5 and 10 mg/kg doses of sudachitin (data not shown), which prompted us to use the 5 mg/kg dose for subsequent investigations.A high-fat diet resulted in significantly elevated total body adipose tissue, increased subcutaneous fat deposits and elevated visceral fat (enlarged epididymal fat pads) which were ameliorated by 5 mg/kg sudachitin administration (Figure 2A–C). However, there were no differences in BAT or muscle weight per body weight among the four groups (data not shown). Sudachitin treatment also significantly reduced adipocyte size in high-fat diet-fed mice, as compared to the vehicle-treated mice fed high-fat diet (Figure 2D and E). Since these changes were independent of food intake and muscle mass, the results suggest that sudachitin improves energy metabolism.We next examined the effects of sudachitin on metabolic parameters. As expected, a high-fat diet significantly increased serum triglyceride and NEFA levels by 1.5- and 1.3-fold, respectively, compared with the control diet (Figure 3A and B). Administration of 5 mg/kg sudachitin prevented these increases in triglyceride and NEFA levels. Total cholesterol levels were not significantly different among any of the studied groups (Figure 3C).

Bottom Line: Flavonoids are effective antioxidants that protect against these chronic diseases.Sudachitin improved dyslipidemia, as evidenced by reduction in triglyceride and free fatty acid levels, and improved glucose tolerance and insulin resistance.The in vitro assay results suggest that sudachitin increased Sirt1 and PGC-1α expression in the skeletal muscle.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Public Health and Applied and Nutrition, Institute of Health Bioscience, University of Tokushima, 3-18-15 Kuramoto, Tokushima 770-8503, Japan.

ABSTRACT

Background: Obesity is a major risk factor for insulin resistance, type 2 diabetes, and stroke. Flavonoids are effective antioxidants that protect against these chronic diseases. In this study, we evaluated the effects of sudachitin, a polymethoxylated flavonoid found in the skin of the Citrus sudachi fruit, on glucose, lipid, and energy metabolism in mice with high-fat diet-induced obesity and db/db diabetic mice. In our current study, we show that sudachitin improves metabolism and stimulates mitochondrial biogenesis, thereby increasing energy expenditure and reducing weight gain.

Methods: C57BL/6 J mice fed a high-fat diet (40% fat) and db/db mice fed a normal diet were treated orally with 5 mg/kg sudachitin or vehicle for 12 weeks. Following treatment, oxygen expenditure was assessed using indirect calorimetry, while glucose tolerance, insulin sensitivity, and indices of dyslipidemia were assessed by serum biochemistry. Quantitative polymerase chain reaction was used to determine the effect of sudachitin on the transcription of key metabolism-regulating genes in the skeletal muscle, liver, and white and brown adipose tissues. Primary myocytes were also prepared to examine the signaling mechanisms targeted by sudachitin in vitro.

Results: Sudachitin improved dyslipidemia, as evidenced by reduction in triglyceride and free fatty acid levels, and improved glucose tolerance and insulin resistance. It also enhanced energy expenditure and fatty acid β-oxidation by increasing mitochondrial biogenesis and function. The in vitro assay results suggest that sudachitin increased Sirt1 and PGC-1α expression in the skeletal muscle.

Conclusions: Sudachitin may improve dyslipidemia and metabolic syndrome by improving energy metabolism. Furthermore, it also induces mitochondrial biogenesis to protect against metabolic disorders.

No MeSH data available.


Related in: MedlinePlus