Added Fructose in Non-Alcoholic Fatty Liver Disease and in Metabolic Syndrome: A Narrative Review - PubMed (original) (raw)

Review

Added Fructose in Non-Alcoholic Fatty Liver Disease and in Metabolic Syndrome: A Narrative Review

Mattia Coronati et al. Nutrients. 2022.

Abstract

Non-alcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease and it is considered the hepatic manifestation of metabolic syndrome (MetS). Diet represents the key element in NAFLD and MetS treatment, but some nutrients could play a role in their pathophysiology. Among these, fructose added to foods via high fructose corn syrup (HFCS) and sucrose might participate in NAFLD and MetS onset and progression. Fructose induces de novo lipogenesis (DNL), endoplasmic reticulum stress and liver inflammation, promoting insulin resistance and dyslipidemia. Fructose also reduces fatty acids oxidation through the overproduction of malonyl CoA, favoring steatosis. Furthermore, recent studies suggest changes in intestinal permeability associated with fructose consumption that contribute to the risk of NAFLD and MetS. Finally, alterations in the hunger-satiety mechanism and in the synthesis of uric acid link the fructose intake to weight gain and hypertension, respectively. However, further studies are needed to better evaluate the causal relationship between fructose and metabolic diseases and to develop new therapeutic and preventive strategies against NAFLD and MetS.

Keywords: HFCS; NAFLD; fructose; metabolic syndrome.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

Hepatic fructose metabolism. In the liver, fructose undergoes KHK phosphorylation to obtain F1P. F1P obtained is metabolized to DHAP and GA by ALDO. DHAP is converted to G3P which enters the lipogenesis mechanisms. On the other hand, GA is converted to GA3P by TK. GA3P can promote lipogenesis after being converted to DHAP, but it can also generate pyruvate, involved, in turn, in the TCA cycle and oxidative phosphorylation to obtain ATP. GA3P is also a precursor of G6P used for gluconeogenesis or glycogenosynthesis. KHK: ketohexokinase; ALDO: aldolase; TK: triose kinase; ATP: adenosine triphosphate; ADP: adenosine diphosphate; F1P: fructose-1-phosphate; DHAP: dihydroxyacetone phosphate; G3P: glycerol 3-phosphate; GA: glyceraldehyde; GA3P: glyceraldehyde 3-phosphate; F1,6P2: fructose-1,6-bisphosphate; F6P: fructose-6-phosphate; G6P: glucose-6-phosphate; TG: triglycerides; TCA: tricarboxylic acid cycle.

Figure 2

Fructose-related pathogenetic pathways in NAFLD and MetS. Fructose promotes NAFLD and MetS via different pathways: (1) it acts as a substrate and inducer of hepatic DNL resulting in steatosis and insulin resistance; (2) it is a precursor of malonyl CoA, an inhibitor of fatty acids oxidation; (3) it increases uric acid synthesis which is associated with hypertension; (4) it induces Apo CIII expression and the secretion of VLDL promoting dyslipidemia; (5) it favors intestinal bacterial translocation resulting in elevated serum LPS levels, closely associated with NAFLD; (6) it causes an incorrect regulation of the hunger–satiety mechanism which favors greater caloric intake and weight gain. HFCS: high fructose corn syrup; DNL: de novo lipogenesis; ER stress: endoplasmic reticulum stress; VLDL: very low-density lipoprotein; Apo CIII: apolipoprotein C-III; TG: triglycerides; FA ox: fatty acids oxidation; LPS: lipopolysaccharide; BP: blood pressure; NAFLD: non-alcoholic fatty liver disease; MetS: metabolic syndrome.

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Added Fructose in Non-Alcoholic Fatty Liver Disease and in Metabolic Syndrome: A Narrative Review - PubMed (original) (raw)