The prophylactic effect of 4-Hydroxyisoleucine derived from fenugreek seeds against high fructose diet induced metabolic dysfunction in growing rats

Abstract

Increased fructose consumption is associated with the development of obesity, dyslipidaemia, diabetic nephropathy and non-alcoholic fatty liver disease (NAFLD). These conditions place a heavy burden on healthcare delivery systems. Phytochemicals are being investigated as alternative management interventions for metabolic disorders. To investigate whether orally administered 4-Hydroxyisoleucine (4-OH-Ile) (derived from fenugreek seeds) could prevent the development of high-fructose-induced metabolic dysfunction in growing rats, eighty weaned rats were grouped (8 males and 8 females per group). In addition to standard rat chow, group I had plain drinking water (PDW); II had 20% fructose solution (20%FS); III had 20%FS+4-OH-Ile (500 mg/kg); IV had PDW+4-OH-Ile; V received 20%FS+Fenofibrate (100 mg/kg) for 10 weeks. In both sexes, there were no significant differences in visceral fat mass and plasma glucose, adiponectin and long bone growth. Diabetic nephropathy histologic assessment showed that females administered 20%FS alone or with Fenofibrate had smaller renal corpuscle areas (p=0.01) compared to controls. All males had smaller renal corpuscles (p=0.0001) compared to those on the normal diet. NAFLD assessment showed that females on the high fructose diet had greater macrovesicular steatosis compared to all other females and greater microvesicular steatosis scores (p=0.01) compared to females administered PDW+4-OH-Ile and 20%FS+Fenofibrate. There were no significant differences in the NAFLD scores of males (p>0.5). There were notable sexually dimorphic responses to the high fructose diet. The 4-OH-Ile was able to prevent the development of diet induced NAFLD in males however 4-OH-Ile was unable to prevent the development of diabetic nephropathy in both sexes