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Nutritional Modulation of Non-Alcoholic Fatty Liver Disease and Insulin Resistance.

Yki-Järvinen H - Nutrients (2015)

Bottom Line: However, any type of caloric restriction seems effective long-term.Overfeeding either saturated fat or carbohydrate increases liver fat content.Vitamin E supplementation decreases liver fat content as well as fibrosis but has no effect on features of insulin resistance.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Helsinki, and Minerva Foundation Institute for Medical Research, Haartmaninkatu 8, 00290 Helsinki, Finland. Hannele.Yki-Jarvinen@helsinki.fi.

ABSTRACT
Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of disorders ranging from simple steatosis (non-alcoholic fatty liver, NAFL) to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFL increases the risk of liver fibrosis. If the liver is fatty due to causes of insulin resistance such as obesity and physical inactivity, it overproduces glucose and triglycerides leading to hyperinsulinemia and a low high-density lipoprotein (HDL) cholesterol concentration. The latter features predispose to type 2 diabetes and cardiovascular disease (CVD). Understanding the impact of nutritional modulation of liver fat content and insulin resistance is therefore of interest for prevention and treatment of NAFLD. Hypocaloric, especially low carbohydrate ketogenic diets rapidly decrease liver fat content and associated metabolic abnormalities. However, any type of caloric restriction seems effective long-term. Isocaloric diets containing 16%-23% fat and 57%-65% carbohydrate lower liver fat compared to diets with 43%-55% fat and 27%-38% carbohydrate. Diets rich in saturated (SFA) as compared to monounsaturated (MUFA) or polyunsaturated (PUFA) fatty acids appear particularly harmful as they increase both liver fat and insulin resistance. Overfeeding either saturated fat or carbohydrate increases liver fat content. Vitamin E supplementation decreases liver fat content as well as fibrosis but has no effect on features of insulin resistance.

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Pathophysiology of “Metabolic NAFLD”, which causes and consequences resemble those of the insulin resistance/metabolic syndrome (MetS). Overeating and physical inactivity predispose to both conditions. Excess glucose, fructose and amino acids are converted to triglyceride (TG) in the liver via de novo lipogenesis (DNL), which pathway is increased in NAFLD [17]. Alterations in gut microbiota in obesity increase gut permeability to bacterial components such as lipopolysaccharide (LPS), which may contribute to inflammation in both adipose tissue and the liver [18]. Overeating leads to adipose tissue expansion, hypoxia, increased fibrosis and cell death. Dead adipocytes are surrounded by macrophages, which produce cytokines such as tumor-necrosis alpha and chemokines such as monocyte chemoattractant protein-1. This impairs the ability of insulin to inhibit lipolysis i.e., inhibit release of free fatty acids (FFA) and leads to deficiency of the insulin-sensitizing cytokine adiponectin. The latter two changes promote synthesis of intrahepatocellular TG. The ability of insulin to suppress glucose and VLDL production is impaired resulting in mild hyperglycemia and hyperinsulinemia, hypertriglyceridemia (TG↑) and a low HDL cholesterol concentration (HDL chol↓). The fatty liver also overproduces many other factors such as the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT), C-reactive protein (CRP) and coagulation factors [13].
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nutrients-07-05454-f001: Pathophysiology of “Metabolic NAFLD”, which causes and consequences resemble those of the insulin resistance/metabolic syndrome (MetS). Overeating and physical inactivity predispose to both conditions. Excess glucose, fructose and amino acids are converted to triglyceride (TG) in the liver via de novo lipogenesis (DNL), which pathway is increased in NAFLD [17]. Alterations in gut microbiota in obesity increase gut permeability to bacterial components such as lipopolysaccharide (LPS), which may contribute to inflammation in both adipose tissue and the liver [18]. Overeating leads to adipose tissue expansion, hypoxia, increased fibrosis and cell death. Dead adipocytes are surrounded by macrophages, which produce cytokines such as tumor-necrosis alpha and chemokines such as monocyte chemoattractant protein-1. This impairs the ability of insulin to inhibit lipolysis i.e., inhibit release of free fatty acids (FFA) and leads to deficiency of the insulin-sensitizing cytokine adiponectin. The latter two changes promote synthesis of intrahepatocellular TG. The ability of insulin to suppress glucose and VLDL production is impaired resulting in mild hyperglycemia and hyperinsulinemia, hypertriglyceridemia (TG↑) and a low HDL cholesterol concentration (HDL chol↓). The fatty liver also overproduces many other factors such as the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT), C-reactive protein (CRP) and coagulation factors [13].

Mentions: Heterogeneity of NAFLD. Although NAFLD is commonly observed in insulin-resistant obese and sometimes insulin-resistant non-obese subjects with the MetS (“Metabolic NAFLD”) (Figure 1), at least two common genetic forms of NAFLD also exist. An allele in PNPLA3 (rs738409[G], encoding I148M, prevalence 30%–50% worldwide) increases liver fat (“PNPLA3 NAFLD”) and the risk of hepatic inflammation and fibrosis, cirrhosis and hepatocellular carcinoma (HCC) [9,10,11,12]. “PNPLA3 NAFLD” is not associated with insulin resistance [10,13]. Another fairly common polymorphism, an E167K variant in (E167K) in TM6SF2 (prevalence 15%) also confers susceptibility to NAFLD (“TM6SF2 NAFLD”) [14]. Carriers with “TM6SF2 NAFLD” are at increased risk of NASH but are not insulin-resistant and their circulating concentrations of triglycerides are normal or subnormal rather than increased [14,15]. Hepatic knockdown of TM6SF2 decreases very low-density lipoprotein (VLDL) secretion [14,16].


Nutritional Modulation of Non-Alcoholic Fatty Liver Disease and Insulin Resistance.

Yki-Järvinen H - Nutrients (2015)

Pathophysiology of “Metabolic NAFLD”, which causes and consequences resemble those of the insulin resistance/metabolic syndrome (MetS). Overeating and physical inactivity predispose to both conditions. Excess glucose, fructose and amino acids are converted to triglyceride (TG) in the liver via de novo lipogenesis (DNL), which pathway is increased in NAFLD [17]. Alterations in gut microbiota in obesity increase gut permeability to bacterial components such as lipopolysaccharide (LPS), which may contribute to inflammation in both adipose tissue and the liver [18]. Overeating leads to adipose tissue expansion, hypoxia, increased fibrosis and cell death. Dead adipocytes are surrounded by macrophages, which produce cytokines such as tumor-necrosis alpha and chemokines such as monocyte chemoattractant protein-1. This impairs the ability of insulin to inhibit lipolysis i.e., inhibit release of free fatty acids (FFA) and leads to deficiency of the insulin-sensitizing cytokine adiponectin. The latter two changes promote synthesis of intrahepatocellular TG. The ability of insulin to suppress glucose and VLDL production is impaired resulting in mild hyperglycemia and hyperinsulinemia, hypertriglyceridemia (TG↑) and a low HDL cholesterol concentration (HDL chol↓). The fatty liver also overproduces many other factors such as the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT), C-reactive protein (CRP) and coagulation factors [13].
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4663582&req=5

nutrients-07-05454-f001: Pathophysiology of “Metabolic NAFLD”, which causes and consequences resemble those of the insulin resistance/metabolic syndrome (MetS). Overeating and physical inactivity predispose to both conditions. Excess glucose, fructose and amino acids are converted to triglyceride (TG) in the liver via de novo lipogenesis (DNL), which pathway is increased in NAFLD [17]. Alterations in gut microbiota in obesity increase gut permeability to bacterial components such as lipopolysaccharide (LPS), which may contribute to inflammation in both adipose tissue and the liver [18]. Overeating leads to adipose tissue expansion, hypoxia, increased fibrosis and cell death. Dead adipocytes are surrounded by macrophages, which produce cytokines such as tumor-necrosis alpha and chemokines such as monocyte chemoattractant protein-1. This impairs the ability of insulin to inhibit lipolysis i.e., inhibit release of free fatty acids (FFA) and leads to deficiency of the insulin-sensitizing cytokine adiponectin. The latter two changes promote synthesis of intrahepatocellular TG. The ability of insulin to suppress glucose and VLDL production is impaired resulting in mild hyperglycemia and hyperinsulinemia, hypertriglyceridemia (TG↑) and a low HDL cholesterol concentration (HDL chol↓). The fatty liver also overproduces many other factors such as the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT), C-reactive protein (CRP) and coagulation factors [13].
Mentions: Heterogeneity of NAFLD. Although NAFLD is commonly observed in insulin-resistant obese and sometimes insulin-resistant non-obese subjects with the MetS (“Metabolic NAFLD”) (Figure 1), at least two common genetic forms of NAFLD also exist. An allele in PNPLA3 (rs738409[G], encoding I148M, prevalence 30%–50% worldwide) increases liver fat (“PNPLA3 NAFLD”) and the risk of hepatic inflammation and fibrosis, cirrhosis and hepatocellular carcinoma (HCC) [9,10,11,12]. “PNPLA3 NAFLD” is not associated with insulin resistance [10,13]. Another fairly common polymorphism, an E167K variant in (E167K) in TM6SF2 (prevalence 15%) also confers susceptibility to NAFLD (“TM6SF2 NAFLD”) [14]. Carriers with “TM6SF2 NAFLD” are at increased risk of NASH but are not insulin-resistant and their circulating concentrations of triglycerides are normal or subnormal rather than increased [14,15]. Hepatic knockdown of TM6SF2 decreases very low-density lipoprotein (VLDL) secretion [14,16].

Bottom Line: However, any type of caloric restriction seems effective long-term.Overfeeding either saturated fat or carbohydrate increases liver fat content.Vitamin E supplementation decreases liver fat content as well as fibrosis but has no effect on features of insulin resistance.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Helsinki, and Minerva Foundation Institute for Medical Research, Haartmaninkatu 8, 00290 Helsinki, Finland. Hannele.Yki-Jarvinen@helsinki.fi.

ABSTRACT
Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of disorders ranging from simple steatosis (non-alcoholic fatty liver, NAFL) to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFL increases the risk of liver fibrosis. If the liver is fatty due to causes of insulin resistance such as obesity and physical inactivity, it overproduces glucose and triglycerides leading to hyperinsulinemia and a low high-density lipoprotein (HDL) cholesterol concentration. The latter features predispose to type 2 diabetes and cardiovascular disease (CVD). Understanding the impact of nutritional modulation of liver fat content and insulin resistance is therefore of interest for prevention and treatment of NAFLD. Hypocaloric, especially low carbohydrate ketogenic diets rapidly decrease liver fat content and associated metabolic abnormalities. However, any type of caloric restriction seems effective long-term. Isocaloric diets containing 16%-23% fat and 57%-65% carbohydrate lower liver fat compared to diets with 43%-55% fat and 27%-38% carbohydrate. Diets rich in saturated (SFA) as compared to monounsaturated (MUFA) or polyunsaturated (PUFA) fatty acids appear particularly harmful as they increase both liver fat and insulin resistance. Overfeeding either saturated fat or carbohydrate increases liver fat content. Vitamin E supplementation decreases liver fat content as well as fibrosis but has no effect on features of insulin resistance.

Show MeSH
Related in: MedlinePlus