J Korean Endocr Soc.  2007 Jun;22(3):192-202. 10.3803/jkes.2007.22.3.192.

The Effect of Fenofibrate and Exercise on Metabolic Syndrome and Hepatic Steatosis in OLETF Rats

• Lee KI
• Kim JM
• Park JY
• Kim JW
• Mok JY
• Park MK
• Lee HJ
• Hong SH
• Li W
• Kim DK

• KMID: 1512031
• DOI: http://doi.org/10.3803/jkes.2007.22.3.192

Abstract

BACKGROUND: The aim of this study is to verify the effects of fenofibrate monotherapy and fenofibrate combined with exercise for improving metabolic syndrome and hepatic steatosis.
METHODS
Thirty-four weeks old OLETF rats (Otsuka Long-Evans Tokushima Fatty Rats, n = 20) were divided four groups: the regular diet group (n = 5, DD group), the exercise group (n = 5, DE group), the fenofibrate (100 mg/kg) treated group (n = 5, DF group) and the combination treatment group {fenofibrate and exercise (n = 5, EF group)}. After 5 weeks of treatment, blood was drawn for measuring the blood glucose, insulin, lipid and leptin levels. All the subjects were sacrificed for assessment of their body adiposity and hepatic steatosis.
RESULTS
The total amount of food intake, body weight and total body weight of the rat were significantly decreased in the EF and DF groups compared to the DD group. The plasma triglyceride and glucose levels were significantly decreased in the EF and DF groups compared to the DD group. The HOMA-IR of EF, DF and DE groups were significantly decreased compared with that of the DD group. The plasma leptin levels of the EF and DF groups were significantly decreased compared with those of the DD and DE groups. The hepatic steatosis index was significantly decreased in the EF and DF groups compared to the DD and DE groups.
CONCLUSION
Fenofibrate monotherapy was effective to control three major components (obesity, hypertriglyceridemia and hyperglycemia) of metabolic syndrome and hepatic steatosis in OLETF rats. Exercise combined with fenofibrate treatment showed an additional effect compared to that of fenofibrate monotherapy.

Keyword

Adiposity; Exercise; Fenofibrate; Insulin resistance; Leptin; Metabolic syndrome; Steatosis

MeSH Terms

Adiposity
Animals
Blood Glucose
Body Weight
Diet
Eating
Fenofibrate*
Glucose
Hypertriglyceridemia
Insulin
Insulin Resistance
Leptin
Plasma
Rats
Rats, Inbred OLETF*
Triglycerides
Blood Glucose
Fenofibrate
Glucose
Insulin
Leptin

Figure

• 

  Fig. 1 The comparison of body weight changes between groups during experiment. DF and EF groups showed markedly decreasing pattern of body weight, but DD and DE groups showed minimal changes. The body weight of LETO group showed increasing pattern. *P < 0.05 vs. DD group; †P < 0.05, vs. DE group.

• 

  Fig. 2 Comparison of each fat pad weight between five groups. DD group showed significantly increased adiposity than control LETO group (P < 0.05). DE group showed significantly decreased epididymal fat weight than DD group (P < 0.05). DF and EF groups also showed significantly decreased each fat pad weight than DD group (P < 0.05). Visceral fat was the sum of mesenteric fat, epididymal fat and retroperitoneal fat. Total fat was the sum of subcutaneous fat and visceral fat. LETO group was compared with only DD group. *P < 0.05 vs. DD group.

• 

  Fig. 3 The correlation between plasma leptin level and body weight in total subjects (A). Fenofibrate does not affect the correlation between two parameters (Compare DD group with DF group). The correlation between plasma leptin level and food intake in total subjects (B). The plasma leptin level of two rats in DF groups (n = 4) showed a tendency to be lowered than expected level.

• 

  Fig. 4 The light microscopic findings of the liver in each group. A, DD group shows moderate hepatic steatosis. The hepatocytes are occupied by macrovesicular fats and showed the ballooning character. B, DE group shows mild hepatic steatosis. Some of the hepatocytes present macrovesicular fats predominantly. C and D, DF group (C) and EF group (D) hardly show recognizable fatty change of hepatocytes. E, LETO group shows normal morphology of hepatocytes. (H-E stain, × 100)

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