Preventive effect of Terminalia bellirica on obesity and metabolic disorders in spontaneously obese type 2 diabetic model mice

Abstract

Visceral obesity induces insulin resistance and is recognized as an important risk factor for metabolic syndrome (MS). Therefore, inhibition of lipid absorption from the intestine is regarded as an effective way of preventing MS. Terminalia bellirica is extensively used in Ayurvedic medicine in India and neighboring countries, and the fruit of this plant has been reported to have hypoglycemic and hypolipidemic effects. In this study, we investigated the preventive effect of a hot water extract of T. bellirica fruit (TB) on obesity and various metabolic disorders, and explored its molecular mechanisms and active ingredients. TB treatment had a preventive effect on obesity, insulin resistance, and hyperlipidemia in spontaneously obese type 2 diabetic TSOD mice. To clarify the molecular mechanisms of TB in preventing obesity, we investigated the inhibitory effect on lipid absorption. TB suppressed absorption of triacylglycerol in an olive oil loading test (in vivo) and showed a strong inhibitory effect on pancreatic lipase activity (in vitro). Furthermore, a search for the active ingredients in TB revealed that gallic acid is the component primarily responsible for the inhibition of pancreatic lipase activity. Thus, our findings indicate that TB could be useful in preventing MS. The mechanisms probably involve suppression of the absorption of meal-derived lipids mediated by gallic acid.

Gallic Acid, the Active Ingredient of <i>Terminalia bellirica</i>, Enhances Adipocyte Differentiation and Adiponectin Secretion

“…33) Considering the gallic acid content of TB, the dose of gallic acid administrated to spontaneously obese type 2 diabetic mice in our previous study is comparable with a dose of 100-300 mg/kg. 24) Therefore, it is reasonable to assume that the gallic acid concentrations (10-30 µM) used here may be consistent with those in mice that were the subject of our previous study. 24) We show here that gallic acid enhanced the expression of the mRNA encoding the marker of adipocyte differentiation Fabp4.…”

“…In our previous study, we found that TB prevented obesity and various metabolic disorders in spontaneously obese type 2 diabetic mice. 24) In particular, TB prevented the accumulation of visceral fat, improved glucose intolerance, and decreased homeostasis model assessment of insulin resistance (HOMA-IR) in these mice, and we therefore focused on adipocytes as a target of TB. We show here that TB enhanced the differentiation of 3T3-L1 preadipocytes in a similar manner to that of the positive control troglitazone.…”

“…24) In brief, 16 g of TB was extracted three times with methanol. The methanol extract (9.23 g) was subjected to normal-phase silica gel column chromatography using a mobile phase containing chloroform, methanol, and distilled water [CHCl 3 Cell Culture 3T3-L1 preadipocytes were maintained in DMEM containing 10% FBS and 1% penicillin/streptomycin at 37°C in a humidified atmosphere containing 5% CO 2 .…”

“…T. bellirica extract has the effects as follows: hypoglycemic, [15][16][17] hypolipidemic, [18][19][20] antihypertensive, 21) antioxidant, 22,23) and antiobesity. 24) Therefore, it is reasonable to speculate that T. bellirica will prevent the symptoms of metabolic syndrome.…”

“…24) Because these findings indicate that TB would directly act on adipocytes, we focused on adipocyte differentiation using mouse 3T3-L1 cells, which are widely used to study adipocyte physiology, to determine the active ingredients of TB and their molecular mechanisms.…”