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Background and aims During fat tolerance tests, plasma triglycerides increase while high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and intermediate-density lipoprotein (IDL) cholesterol decrease. However, it is unknown whether triglyceride content increases and cholesterol content decreases in HDL and LDL + IDL fractions following normal meals in the general population. Therefore, we tested the hypothesis that triglyceride content increases while cholesterol content decreases in HDL and LDL + IDL fractions following normal meals. Methods In this cross-sectional study, we included 25,656 individuals aged 20–100 years, all without lipid-lowering therapy at examination and selected for metabolomic profiling from the Copenhagen General Population Study. Triglyceride and cholesterol content of 14 lipoprotein fractions weas measured using nuclear magnetic resonance (NMR) spectroscopy. Time since last meal was recorded by the examiner immediately before blood sampling. Results Following normal meals in age and sex-adjusted analyses and when compared with fasting levels, plasma triglycerides were higher for up to 5–6 h, and triglyceride content was higher for up to 6–7 h in HDL fractions, for up to 6–7 h in LDL + IDL fractions, and for up to 5–6 h in very-low-density lipoprotein (VLDL) fractions. Further, plasma cholesterol was lower for up to 2–3 h, and cholesterol content was lower for up to 0–1 h in HDL fractions and for up to 4–5 h in LDL + IDL fractions, while cholesterol content was higher for up to 4–5 h in VLDL fractions. Conclusions Following normal meals, triglyceride content increases while cholesterol content decreases in HDL and LDL + IDL fractions., Background and aims: During fat tolerance tests, plasma triglycerides increase while high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and intermediate-density lipoprotein (IDL) cholesterol decrease. However, it is unknown whether triglyceride content increases and cholesterol content decreases in HDL and LDL + IDL fractions following normal meals in the general population. Therefore, we tested the hypothesis that triglyceride content increases while cholesterol content decreases in HDL and LDL + IDL fractions following normal meals. Methods: In this cross-sectional study, we included 25,656 individuals aged 20–100 years, all without lipid-lowering therapy at examination and selected for metabolomic profiling from the Copenhagen General Population Study. Triglyceride and cholesterol content of 14 lipoprotein fractions weas measured using nuclear magnetic resonance (NMR) spectroscopy. Time since last meal was recorded by the examiner immediately before blood sampling. Results: Following normal meals in age and sex-adjusted analyses and when compared with fasting levels, plasma triglycerides were higher for up to 5–6 h, and triglyceride content was higher for up to 6–7 h in HDL fractions, for up to 6–7 h in LDL + IDL fractions, and for up to 5–6 h in very-low-density lipoprotein (VLDL) fractions. Further, plasma cholesterol was lower for up to 2–3 h, and cholesterol content was lower for up to 0–1 h in HDL fractions and for up to 4–5 h in LDL + IDL fractions, while cholesterol content was higher for up to 4–5 h in VLDL fractions. Conclusions: Following normal meals, triglyceride content increases while cholesterol content decreases in HDL and LDL + IDL fractions.

Metabolic-associated fatty liver disease (MAFLD), the main cause of chronic liver disease worldwide, is a progressive disease ranging from fatty liver to steatohepatitis (metabolic-associated steatohepatitis; MASH). Nevertheless, it remains underdiagnosed due to the lack of effective non-invasive methods for its diagnosis and staging. Although MAFLD has been found in lean individuals, it is closely associated with obesity-related conditions. Adipose tissue is the main source of liver triglycerides and adipocytes act as endocrine organs releasing a large number of adipokines and pro-inflammatory mediators involved in MAFLD progression into bloodstream. Among the adipocyte-derived molecules, fatty acid binding protein 4 (FABP4) has been recently associated with fatty liver and additional features of advanced stages of MAFLD. Additionally, emerging data from preclinical studies propose FABP4 as a causal actor involved in the disease progression, rather than a mere biomarker for the disease. Therefore, the FABP4 regulation could be considered as a potential therapeutic strategy to MAFLD. Here, we review the current knowledge of FABP4 in MAFLD, as well as its potential role as a therapeutic target for this disease.

Amyloid deposits in pancreatic islets, mainly formed by human islet amyloid polypeptide (hIAPP) aggregation, have been associated with loss of beta -cell mass and function, and are a pathological hallmark of type 2 diabetes (T2D). Treatment with chaperones has been associated with a decrease in endoplasmic reticulum stress leading to improved glucose metabolism. The aim of this work was to investigate whether the chemical chaperone 4-phenylbutyrate (PBA) prevents glucose metabolism abnormalities and amyloid deposition in obese agouti viable yellow (A(vy)) mice that overexpress hIAPP in beta cells (A(vy) hIAPP mice), which exhibit overt diabetes. Oral PBA treatment started at 8 weeks of age, when A(vy) hIAPP mice already presented fasting hyperglycemia, glucose intolerance, and impaired insulin secretion. PBA treatment strongly reduced the severe hyperglycemia observed in obese A(vy) hIAPP mice in fasting and fed conditions throughout the study. This effect was paralleled by a decrease in hyperinsulinemia. Importantly, PBA treatment reduced the prevalence and the severity of islet amyloid deposition in A(vy) hIAPP mice. Collectively, these results show that PBA treatment elicits a marked reduction of hyperglycemia and reduces amyloid deposits in obese and diabetic mice, highlighting the potential of chaperones for T2D treatment.