Lipoprotein lipase (LPL) plays a central role in incorporating plasma lipids into tissues and regulates lipid metabolism and energy balance in the human body. Conversely, LPL expression is almost absent in normal adult livers. Therefore, its physiological role in the liver remains unknown. We aimed to elucidate the role of LPL in the pathophysiology of nonalcoholic steatohepatitis (NASH), a hepatic manifestation of obesity. Hepatic stellate cell (HSC)–specific LPL‐knockout (LplHSC‐KO) mice, LPL‐floxed (Lplfl/fl) mice, or double‐mutant toll‐like receptor 4–deficient (Tlr4−/−) LplHSC‐KO mice were fed a high‐fat/high‐cholesterol diet for 4 weeks to establish the nonalcoholic fatty liver model or an high‐fat/high‐cholesterol diet for 24 weeks to establish the NASH model. Human samples, derived from patients with nonalcoholic fatty liver disease, were also examined. In human and mouse NASH livers, serum obesity‐related factors, such as free fatty acid, leptin, and interleukin‐6, dramatically increased the expression of LPL, specifically in HSCs through signal transducer and activator of transcription 3 signaling, as opposed to that in hepatocytes or hepatic macrophages. In the NASH mouse model, liver fibrosis was significantly reduced in LplHSC‐KO mice compared with that in Lplfl/fl mice. Nonenzymatic LPL‐mediated cholesterol uptake from serum lipoproteins enhanced the accumulation of free cholesterol in HSCs, which amplified TLR4 signaling, resulting in the activation of HSCs and progression of hepatic fibrosis in NASH. Conclusion: The present study reveals the pathophysiological role of LPL in the liver, and furthermore, clarifies the pathophysiology in which obesity, as a background factor, exacerbates NASH. The LPL‐mediated HSC activation pathway could be a promising therapeutic target for treating liver fibrosis in NASH.

A prospective study was performed in the Reproduction Center of Ichikawa General Hospital (Chiba, Japan) to assess the relationship between dyslipidaemia and sperm quality and serum hormone levels in male patients in Japan. The semen parameters and blood samples were assessed in relation to several variables, including body mass index (BMI) and serum triglyceride (TG) levels. Between 2011 and 2012, 167 male partners of infertile couples aged 22-46 years (mean: 36.5 years) were referred to the reproduction centre. In total, 66 patients (39.5%) had hypertriglyceridaemia (TG level ≥ 150 mg dl(-1) ). There was no significant relationship between serum TG levels and sperm concentration or motility; however, the serum TG level was positively associated with the sperm morphological traits. Furthermore, the serum levels of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase were associated with the serum TG levels. By contrast, a negative relationship between serum testosterone and TG levels was discovered.

Aim Chitinase 3‐like 1 (CHI3L1), an 18‐glycosyl hydrolase‐related molecule, is a member of the enzymatically inactive chitinase‐like protein family. Serum levels of CHI3L1 are strongly correlated with hepatic fibrosis progression during many liver diseases. Therefore, this protein could be involved in the development of hepatic fibrosis pathology; however, its role has not been elucidated. We aimed to elucidate its role in the pathophysiology of liver fibrosis. Methods Chitinase 3‐like 1‐deficient (Chi3l1−/−) mice were given carbon tetrachloride twice per week for 4 weeks or fed a methionine choline‐deficient diet for 12 weeks to generate mouse liver fibrosis models. Human fibrotic liver tissues were also examined immunohistochemically. Results In human and mouse fibrotic livers, CHI3L1 expression was mainly localized to hepatic macrophages, and the intrahepatic accumulation of CHI3L1+ macrophages was significantly enhanced compared to that in control livers. In the two mouse models, hepatic fibrosis was significantly ameliorated in Chi3l1−/− mice compared to that in wild‐type mice, which was dependent on hepatic macrophages. The accumulation and activation of hepatic macrophages was also significantly suppressed in Chi3l1−/− mice compared to that in wild‐type mice. Furthermore, apoptotic hepatic macrophages were significantly increased in Chi3l1−/− mice. Chitinase 3‐like 1 was found to inhibit hepatic macrophage apoptosis by suppressing Fas expression and activating Akt signaling in an autocrine manner, which resulted in hepatic macrophage accumulation and activation, exaggerating liver fibrosis. Conclusions Chitinase 3‐like 1 exacerbates liver fibrosis progression by suppressing apoptosis in hepatic macrophages. Therefore, this might be a potential therapeutic target for the treatment of liver fibrosis.

Background and AimDietary emulsifiers are widely used in processed foods and officially approved as safe for intake. However, recent studies have demonstrated that some emulsifiers alter the colonic microbiota, leading to colonic low‐grade inflammation, in mice. The effect of dietary emulsifiers on small‐intestinal microbiota, which is important for gut immunity, has not been studied. We aimed to investigate the effect of a representative dietary emulsifier, polysorbate‐80 (P80), on the small‐intestinal microbiota in normal mice.MethodsSome mice were pretreated with P80 for 8 weeks with or without indomethacin administration on the last 2 days, and intestinal damage was evaluated histologically. The ileal and colonic microbiota composition was assessed using 16S rRNA polymerase chain reaction.ResultsPolysorbate‐80 increased the Gammaproteobacteria abundance and decreased the α‐diversity in the small intestine. No decrease in α‐diversity was observed in the colon. P80 pretreatment exacerbated the indomethacin‐induced small‐intestinal lesions and significantly increased the interleukin‐1β expression. Culture of ileal content on deoxycholate hydrogen sulfide lactose agar showed that P80 significantly increased the colonies of the sulfide‐producing bacteria Proteus spp. (genetically identified as Proteus mirabilis). Antibiotic pretreatment abolished the P80‐induced aggravation of indomethacin‐induced ileitis. Motility assay in semisolid agar showed that adding 0.02% P80 to the agar significantly increased the diameter of P. mirabilis colonies but not that of Escherichia coli colonies.ConclusionsPolysorbate‐80 enhances the vulnerability of the small intestine to indomethacin‐induced injury by inducing ileal dysbiosis. Direct enhancement of the motility of specific flagellated microbiota by P80 might be related to dysbiosis and intestinal injury.

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