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High fat diet (HFD) feeding or leptin deficient mice are extensively used as models resembling features of human non-alcoholic fatty liver disease (NAFLD). The concurrence of experimental factors as fat content and source or total caloric intake leads to prominent differences in the development of the hepatic steatosis and related disturbances. In this work, we characterized the hepatic lipid accumulation induced by HFD in wild type (Wt) and ob/ob mice with the purpose of differentiating adaptations to HFD from those specific of increased overfeeding due to leptin deficiency-associated hyperphagia. Given that most published works have been done in male models, we used female mice with the aim of increasing the body of evidence regarding NAFLD in female subjects. HFD promoted liver lipid accumulation only in the hyperphagic strain. Nevertheless, a decrease of lipid droplet-associated cholesteryl ester (CE) in both Wt and obese animals was observed. These changes were accompanied by an improvement in the profile of lipoproteins that transport cholesterol and liver function markers in plasma from ob/ob mice and a lower hepatic index. Using primary hepatocytes from female mice, over accumulation of CE induced by 0.4 mM oleic acid reversed in the presence of a specific Takeda G-protein-coupled bile acid receptor (TGR5) agonist. Nevertheless, hepatocytes from male mice were not responsive. This study suggests that enterohepatic circulation of bile acids might be one of the factors that can affect sex dimorphism in NAFLD development, which underlines the importance of including female models in NAFLD research field.

The innate immune response to pathogens during the acute phase response includes lipid metabolism adaptations. Hepatic triacylglycerol (TG) and cholesteryl ester (CE) storage in and mobilization from lipid droplets (LDs) respond to metabolic changes under the control of liver X receptor (LXR) transactivation and cytokine transduction. To evaluate whether alterations of these mechanisms have an impact in the adaptive response to endotoxemia, we analysed liver metabolism changes in lipopolysaccharide (LPS)-treated ob/ob mice, which show altered metabolic and innate responses and a higher sensitivity to sepsis. Lipid composition of serum lipoproteins and hepatic LDs was determined in wild type and ob/ob mice 24 h after LPS treatment. Liver metabolic profiling was done by measuring enzyme activities and mRNA levels. Increased CE hydrolase activity in LDs from endotoxemic mice was accompanied by a lower content of CE and low or no induction of LXR-mediated expression of genes involved in HDL secretion. The attenuated response in liver lipid mobilization accompanied by the strain-specific cholesterol enrichment of secreted VLDL might lead to accumulation of LDL cholesterol. According to our findings, obese leptin-deficient mice present an altered control of hepatic lipid metabolism responses to LPS, which might be, in part at least, a consequence of impaired LXR.

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Introduction: Hepatitis B surveillance is crucial. We proposed to describe the seroprevalence of Hepatitis B infection and the associated factors among Ecuadorian Amazonia communities. Outline: A serologic cross-sectional study was carried out in subjects over two years old. We classified seropositivity according to the Centers of Diseases Control criteria and recorded sex, age, temporary migration, sometime Hepatitis B in their life, and previous vaccination. Results: Out of 215 participants, 50.0%, 8.8%, 1.9%, and 1.4% were susceptible, immune due to natural infection, chronic infection, and early acute HBV infection, respectively. Of the 8 people who reported having ever been diagnosed with Hepatitis B, none showed chronic or acute infection and one was positive for immunity due to the vaccine. HBsAg was found in 3.3% (95% IC 0.9-7.0) and was higher among those who migrate 7.7% (p-value 0.04). 16.3% (95% CI 11.6-21.4) was immune due to HBV vaccination. Among the 58 participants who declared having received the vaccine, 20.7% presented post-vaccine immunity. Implications: Participants who should have benefited from the vaccination campaign (susceptible) are those with the lowest immune response due to vaccination. To assessing the burden of viral hepatitis in people living in marginalized areas and guide preventive measures is mandatory.