Fatty liver (FL), also known as hepatic steatosis, is strongly associated with chronic liver disease and with prominent metabolic morbidity. Although a few rare genetic dispositions have been identified, FL generally develops in humans on the background of over-nutrition and sedentary lifestyle. Ruminants are also susceptible to the development of FL disease; however, this is generally due to insufficient dietary energy common to the transition period from late pregnancy to early lactation. Whether ruminants can develop hepatic steatosis due to excess caloric intake is currently unknown. In preliminary experiments, we found that feeding lambs an energy-rich carbohydrate-based diet induced hyperglycemia. To investigate the long-term metabolic and liver-related implications of such dietary hyperglycemia, lambs were raised on a carbohydrateenergy-rich diet for four months. The grown lambs developed symptoms of metabolic morbidity, such as hyperglycemia, insulin resistance and dyslipidemia, as well as hepatomegaly and FL. In addition, the observations suggested, unlike commonly though, that hepatic de novo lipogenesis was more dominant than adipose lipolysis for the accumulation of liver fat. The development of metabolic syndrome-like features along with liver-related abnormalities, suggest the suitability of sheep as a large-animal model for FL and metabolic disorders emanating from excessive caloric intake.
Fatty liver (FL), also known as hepatic steatosis, is strongly associated with chronic liver disease and with prominent metabolic morbidity. Although a few rare genetic dispositions have been identified, FL generally develops in humans on the background of over-nutrition and sedentary lifestyle. Ruminants are also susceptible to the development of FL disease; however, this is generally due to insufficient dietary energy common to the transition period from late pregnancy to early lactation. Whether ruminants can develop hepatic steatosis due to excess caloric intake is currently unknown. In preliminary experiments, we found that feeding lambs an energy-rich carbohydrate-based diet induced hyperglycemia. To investigate the long-term metabolic and liver-related implications of such dietary hyperglycemia, lambs were raised on a carbohydrateenergy-rich diet for four months. The grown lambs developed symptoms of metabolic morbidity, such as hyperglycemia, insulin resistance and dyslipidemia, as well as hepatomegaly and FL. In addition, the observations suggested, unlike commonly though, that hepatic de novo lipogenesis was more dominant than adipose lipolysis for the accumulation of liver fat. The development of metabolic syndrome-like features along with liver-related abnormalities, suggest the suitability of sheep as a large-animal model for FL and metabolic disorders emanating from excessive caloric intake.