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The Impact of Macronutrient Intake on Non-alcoholic Fatty Liver Disease (NAFLD): Too Much Fat, Too Much Carbohydrate, or Just Too Many Calories?

ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is a growing epidemic, in parallel with the obesity crisis, rapidly becoming one of the commonest causes of chronic liver disease worldwide. Diet and physical activity are important determinants of liver fat accumulation related to insulin resistance, dysfunctional adipose tissue, and secondary impaired lipid storage and/or increased lipolysis. While it is evident that a hypercaloric diet (an overconsumption of calories) promotes liver fat accumulation, it is also clear that the macronutrient composition can modulate this risk. A number of other baseline factors modify the overfeeding response, which may be genetic or environmental. Although it is difficult to disentangle the effects of excess calories vs. specifically the individual effects of excessive carbohydrates and/or fats, isocaloric, and hypercaloric dietary intervention studies have been implemented to provide insight into the effects of different macronutrients, sub-types and their relative balance, on the regulation of liver fat. What has emerged is that different types of fat and carbohydrates differentially influence liver fat accumulation, even when diets are isocaloric. Furthermore, distinct molecular and metabolic pathways mediate the effects of carbohydrates and fat intake on hepatic steatosis. Fat accumulation appears to act through impairments in lipid storage and/or increased lipolysis, whereas carbohydrate consumption has been shown to promote liver fat accumulation through de novo lipogenesis. Effects differ dependent upon carbohydrate and fat type. Saturated fat and fructose induce the greatest increase in intrahepatic triglycerides (IHTG), insulin resistance, and harmful ceramides compared with unsaturated fats, which have been found to be protective. Decreased intake of saturated fats and avoidance of added sugars are therefore the two most important dietary interventions that can lead to a reduction in IHTG and potentially the associated risk of developing type 2 diabetes. A healthy and balanced diet and regular physical activity must remain the cornerstones of effective lifestyle intervention to prevent the development and progression of NAFLD. Considering the sub-type of each macronutrient, in addition to the quantity, are critical determinants of liver health.

SUBMITTER: Hydes T

PROVIDER: S-EPMC7921724 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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The Impact of Macronutrient Intake on Non-alcoholic Fatty Liver Disease (NAFLD): Too Much Fat, Too Much Carbohydrate, or Just Too Many Calories?

Hydes Theresa T Alam Uazman U Cuthbertson Daniel J DJ

Frontiers in nutrition 20210216

Non-alcoholic fatty liver disease (NAFLD) is a growing epidemic, in parallel with the obesity crisis, rapidly becoming one of the commonest causes of chronic liver disease worldwide. Diet and physical activity are important determinants of liver fat accumulation related to insulin resistance, dysfunctional adipose tissue, and secondary impaired lipid storage and/or increased lipolysis. While it is evident that a hypercaloric diet (an overconsumption of calories) promotes liver fat accumulation, ...[more]

PMID: 33665203

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Project description:Vitamin A is required for important physiological processes, including embryogenesis, vision, cell proliferation and differentiation, immune regulation, and glucose and lipid metabolism. Many of vitamin A's functions are executed through retinoic acids that activate transcriptional networks controlled by retinoic acid receptors (RARs) and retinoid X receptors (RXRs).The liver plays a central role in vitamin A metabolism: (1) it produces bile supporting efficient intestinal absorption of fat-soluble nutrients like vitamin A; (2) it produces retinol binding protein 4 (RBP4) that distributes vitamin A, as retinol, to peripheral tissues; and (3) it harbors the largest body supply of vitamin A, mostly as retinyl esters, in hepatic stellate cells (HSCs). In times of inadequate dietary intake, the liver maintains stable circulating retinol levels of approximately 2 ?mol/L, sufficient to provide the body with this vitamin for months. Liver diseases, in particular those leading to fibrosis and cirrhosis, are associated with impaired vitamin A homeostasis and may lead to vitamin A deficiency. Liver injury triggers HSCs to transdifferentiate to myofibroblasts that produce excessive amounts of extracellular matrix, leading to fibrosis. HSCs lose the retinyl ester stores in this process, ultimately leading to vitamin A deficiency. Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and is a spectrum of conditions ranging from benign hepatic steatosis to non-alcoholic steatohepatitis (NASH); it may progress to cirrhosis and liver cancer. NASH is projected to be the main cause of liver failure in the near future. Retinoic acids are key regulators of glucose and lipid metabolism in the liver and adipose tissue, but it is unknown whether impaired vitamin A homeostasis contributes to or suppresses the development of NAFLD. A genetic variant of patatin-like phospholipase domain-containing 3 (PNPLA3-I148M) is the most prominent heritable factor associated with NAFLD. Interestingly, PNPLA3 harbors retinyl ester hydrolase activity and PNPLA3-I148M is associated with low serum retinol level, but enhanced retinyl esters in the liver of NAFLD patients. Low circulating retinol in NAFLD may therefore not reflect true "vitamin A deficiency", but rather disturbed vitamin A metabolism. Here, we summarize current knowledge about vitamin A metabolism in NAFLD and its putative role in the progression of liver disease, as well as the therapeutic potential of vitamin A metabolites.

Dataset Information

The Impact of Macronutrient Intake on Non-alcoholic Fatty Liver Disease (NAFLD): Too Much Fat, Too Much Carbohydrate, or Just Too Many Calories?

Publications

The Impact of Macronutrient Intake on Non-alcoholic Fatty Liver Disease (NAFLD): Too Much Fat, Too Much Carbohydrate, or Just Too Many Calories?

Similar Datasets

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