Effects of Botryosphaeran, β‐(1→3)(1→6)‐D‐Glucan, on Hepatic Steatosis and Dyslipidemia Present in Obese‐Rats

Epidemiological studies have associated obesity with the development of other diseases like dyslipidemia, hepatic steatosis, diabetes and cancer. Some factors frequently present in obesity, like insulin resistance and hyperinsulinemia, can contribute to the development of these comorbidities. β‐glucans are substances present in some foods, like corn and cereals, and produced by microorganisms, including bacteria and fungus, and they are described to be effective in treating several pathological conditions including microbial infections, hypercholesterolemia, diabetes and cancer. Our previous work showed that botryosphaeran, a β‐ (1→3)(1→6)‐D‐glucan, produced by the fungus, Botryosphaeria rhodina , exhibits hypoglycemic and hypocholesterolemic effects. However the mechanisms involved remained to be determined. Thus, the objective of this study was to analyze the effects of botryosphaeran on insulin resistance, glucose tolerance, dyslipidemia and hepatic steatosis, present in obesity induced by high‐fat and high‐sugar diet in rats, and analyze the mechanism of action of botryosphaeran on it. Obesity was induced in rats by ingestion of high‐fat chow and water with sucrose (300 g/L) for 8 weeks. Control rats received standard rodent chow. On the 6 th week, it was started the treatment with botryosphaeran (12 mg/kg b.w., once daily, by gavage, for 15 days). The respective controls (control and obese) received distilled water. Thus, the rats were divided into 3 groups:Control (C), Obese (O) and Obese treated with botryosphaeran (OB). On the 8 th week, the glucose tolerance, dyslipidemia, hepatic steatosis and botryosphaeran effect were analyzed. The obesity was characterized by the adiposity index=[(periepididymal+retroperitoneal+visceral fat) / body weight × 100] and determining the relative weight of fat, muscles and liver. Furthermore, we analyzed the glucose and lipid profile, glucose tolerance, as well as the concentration of glycogen and lipids in the liver. Protein expression was determined by Western blotting. Obese rats showed a significant increase in weight gain, adiposity index, retroperitoneal, visceral and periepididymal adipose tissue, as well as, showed a reduced glucose tolerance. In addition, obese rats presented dyslipidemia and hepatic steatosis, observed by the increase in lipid levels in the serum and liver. Botryosphaeran significantly reduced feed intake, weight gain (g;C=21.4±17.0; O=67.5±27.4* and OB=23.2±15.2 # ), periepididymal and visceral adipose tissue, and improved significantly glucose tolerance. Furthermore, botryosphaeran reduced the serum levels of triglycerides (mg/dL;C=96.9±41.1; O=169.2±57.7* and OB=77.9±13.8 # ) and very low density lipoprotein (VLDL‐C) (mg/dl;C=19.4±8.2; O=33.8±11.5* and OB=15.57±2.8 # ), and increased the levels of high density lipoprotein (HDL‐C) cholesterol (mg/dl;C=32.9±1.8; O=30.0±1.6* and OB=34.1±1.7 # ), as well as, increased the content of glycogen in the liver (mg glucose/g liver; C=3.2±0.8; O=6.0±1.8* and OB=7.7±1.4*). Treatment of obese rats with botryosphaeran also reduced the levels of total lipids (mg/g liver; C=29.8±4.6; O=49.4±5.7* and OB=41.9±4.1 # ), triglycerides and total cholesterol in the liver, and increased AMPK activity in adipose tissue. Thus, our data allow us to conclude that botryosphaeran, reducing the stimulatory effect of obesity on dyslipidemia and hepatic steatosis, has a potential role in the management of obesity comorbidities. Support or Funding Information The authors are grateful to Fundação de Amparo à Pesquisa do Estado de Mato Grosso (FAPEMAT), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação Araucária for the financial support.