Calorie restricted high protein diets downregulate lipogenesis and lower intrahepatic triglyceride concentrations in male rats

Authors: MARGOLIS, LEE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; RIVAS, DONATO - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; EZZYAT, YASSINE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; GAFFNEY-STOMBERG, ERIN - Us Army Research Institute Of Environmental Medicine; YOUNG, ANDREW - Us Army Research Institute Of Environmental Medicine; MCCLUNG, JAMES - Us Army Research Institute Of Environmental Medicine; FIELDING, ROGER - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; STEFAN, PASIAKOS - Us Army Research Institute Of Environmental Medicine

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/12/2016
Publication Date: 9/15/2016
Citation: Margolis, L., Rivas, D.A., Ezzyat, Y., Gaffney-Stomberg, E., Young, A.J., McClung, J.P., Fielding, R.A., Stefan, P.A. 2016. Calorie restricted high protein diets downregulate lipogenesis and lower intrahepatic triglyceride concentrations in male rats. Nutrients. 8(9):E571. https://doi.org/10.3390/nu8090571.

Interpretive Summary: Excess fat in the liver may lead to (or exacerbate existing) peripheral insulin resistance and high fat and lipid levels in blood. These metabolic dysfunctions are associated with the accumulation of total body fat, and, if left untreated, can result in nonalcoholic fatty liver disease, type 2 diabetes and cardiovascular disease. This study demonstrated that calorie restriction and higher-protein/lower-carbohydrate diets independently reduce molecular markers in liver regulating fat synthesis, which results in an apparent synergistic benefit by reducing triglyceride concentrations in liver. These data suggest that combining restricted carbohydrate and elevated dietary protein intake during periods of calorie restriction may target multiple metabolic processes that may improve long-term health.

Technical Abstract: The purpose of this investigation was to assess the influence of calorie restriction (CR) alone, higher-protein/lower-carbohydrate intake alone, and combined CR higher-protein/lower-carbohydrate intake on glucose homeostasis, hepatic de novo lipogenesis (DNL), and intrahepatic triglycerides. Twelve-week old male Sprague Dawley rats consumed ad libitum (AL) or CR (40% restriction), adequate (10%), or high (32%) protein (PRO) milk-based diets for 16 weeks. Metabolic profiles were assessed in serum, and intrahepatic triglyceride concentrations and molecular markers of de novo lipogenesis were determined in liver. Independent of calorie intake, 32% PRO tended to result in lower homeostatic model assessment of insulin resistance (HOMA-IR) values compared to 10% PRO, while insulin and homeostatic model assessment of B-cell function (HOMA-B) values were lower in CR than AL, regardless of protein intake. Intrahepatic triglyceride concentrations were 27.4 +/- 4.5 and 11.7 +/- 4.5 micromole x g(-1) lower (p < 0.05) in CR and 32% PRO compared to AL and 10% PRO, respectively. Gene expression of fatty acid synthase (FASN), stearoyl-CoA destaurase-1 (SCD1) and pyruvate dehydrogenase kinase, isozyme 4 (PDK4) were 45% +/- 1%, 23% +/- 1%, and 57% +/- 1% lower (p < 0.05), respectively, in CR than AL, regardless of protein intake. Total protein of FASN and SCD were 50% +/- 1% and 26% +/- 1% lower (p < 0.05) in 32% PRO compared to 10% PRO, independent of calorie intake. Results from this investigation provide evidence that the metabolic health benefits associated with CR-specifically reduction in intrahepatic triglyceride content-may be enhanced by consuming a higher-protein/lower-carbohydrate diet.