Key result
Apolipoprotein CIII overexpression in mice induced NAFLD-like features and, with a high-fat diet, led to marked increases in plasma TNFα (8-fold) and IL-6 (60%).
ApoCIII overexpression and hypertriglyceridemia play a major role in liver inflammation and cell death, increasing susceptibility to diet-induced NAFLD, with inflammation persisting despite fenofibrate treatment.
ApoCIII may promote diet-independent NAFLD-like changes; hypothesis-generating in mice, leaves open human relevance.
Nonalcoholic fatty liver disease (NAFLD) is the principal manifestation of liver disease in obesity and metabolic syndrome. By comparing hypertriglyceridemic transgenic mice expressing apolipoprotein (apo) CIII with control nontransgenic (NTg) littermates, we demonstrated that overexpression of apoCIII, independent of a high‐fat diet (HFD), produces NAFLD‐like features, including increased liver lipid content; decreased antioxidant power; increased expression of TNFα, TNFα receptor, cleaved caspase‐1, and interleukin‐1β; decreased expression of adiponectin receptor‐2; and increased cell death. This phenotype is aggravated and additional NAFLD features are differentially induced in apoCIII mice fed a HFD. HFD induced glucose intolerance together with increased gluconeogenesis, indicating hepatic insulin resistance. Additionally, the HFD led to marked increases in plasma TNFα (8‐fold) and IL‐6 (60%) in apoCIII mice. Cell death signaling (Bax/Bcl2), effector (caspase‐3), and apoptosis were augmented in apoCIII mice regardless of whether a HFD or a low‐fat diet was provided. Fenofibrate treatment reversed several of the effects associated with diet and apoCIII expression but did not normalize inflammatory traits even when liver lipid content was fully corrected. These results indicate that apoCIII and/or hypertriglyceridemia plays a major role in liver inflammation and cell death, which in turn increases susceptibility to and the severity of diet‐induced NAFLD.
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Paiva et al. (2017) studied Nonalcoholic fatty liver disease (NAFLD). Apolipoprotein CIII overexpression vs. Control nontransgenic (NTg) littermates was evaluated on NAFLD-like features including liver lipid content, inflammation, and cell death. Apolipoprotein CIII overexpression in mice induced NAFLD-like features and, with a high-fat diet, led to marked increases in plasma TNFα (8-fold) and IL-6 (60%).
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