The liver is one of the first organs affected by accumulated ectopic lipids. Increased de novo lipogenesis and excessive triglyceride accumulation in the liver are hallmarks of nonalcoholic fatty liver disease (NAFLD) and are strongly associated with obesity, insulin resistance, and type 2 diabetes. Maqui dietary supplemented diet-induced obese mice showed better insulin response and decreased weight gain. We previously described that these positive effects of maqui are partially due to an induction of a brown-like phenotype in subcutaneous white adipose tissue that correlated with a differential expression of Chrebp target genes. In this work, we aimed to deepen the molecular mechanisms underlying the impact of maqui on the onset and development of the obese phenotype and insulin resistance focusing on liver metabolism. Our results showed that maqui supplementation decreased hepatic steatosis caused by a high-fat diet. Changes in the metabolic profile include a downregulation of the lipogenic liver X receptor (LXR) target genes and of fatty acid oxidation gene expression together with an increase in the expression of small heterodimer partner interacting leucine zipper protein (Smile), a corepressor of the nuclear receptor family. Our data suggest that maqui supplementation regulates lipid handling in liver to counteract the metabolic impact of a high-fat diet.

Obesity is a worldwide epidemic with severe metabolic consequences. Polyphenols are secondary metabolites in plants and the most abundant dietary antioxidants, which possess a wide range of health effects. The most relevant food sources are fruit and vegetables, red wine, black and green tea, coffee, virgin olive oil, and chocolate, as well as nuts, seeds, herbs, and spices. The aim of this work was to evaluate the ability of a pure, isolated polyphenol supplementation to counteract the pernicious metabolic effects of a high-fat diet (HFD). Our results indicated that the administration of pure, isolated polyphenols under HFD conditions for 26 weeks worsened the glucose metabolism in diet-induced obese mice. The data showed that the main target organ for these undesirable effects were the kidneys, where we observed fibrotic, oxidative, and kidney-disease markers. This work led us to conclude that the administration of pure polyphenols as a food supplement would not be advisable. Instead, the ingestion of complete “whole” foods would be the best way to get the health effects of bioactive compounds such as polyphenols.

Fibroblast growth factor 21 (FGF21) is a key hormone for metabolic homeostasis under conditions such as obesity, aging and diabetes. While extensively studied in males, its role in female physiology remains poorly defined. This study evaluated the effects of hepatic FGF21 deletion in 12-month-old female mice using a liver-specific FGF21 knockout (FKO) model. FKO females exhibited reduced body weight and improved glucose tolerance, with no changes in circulating FGF21 levels. In the liver, RT-qPCR analysis showed that the expression of genes involved in de novo lipogenesis, including Srebp1c, Fasn, and Scd1, was downregulated, whereas markers of fatty acid uptake (Cd36) and β-oxidation (Cpt1a) were upregulated without alterations in hepatic triglyceride content and lower levels of serum adiponectin. Remarkably, telomere length in both liver and adipose tissue was preserved, indicating improved cellular aging. Hepatic transcriptomic analysis revealed a global downregulation of genes linked to cytoskeletal organization, immune processes and fibrosis. Among these, Chrna4, a hepatocyte-specific nicotinic acetylcholine receptor subunit implicated in protection against metabolic-associated steatohepatitis (MASH), was significantly reduced. These findings suggest that hepatic FGF21 deficiency in aged female mice promotes metabolic health by limiting pro-inflammatory and fibrotic pathways and preserving telomere integrity, with Chrna4 emerging as a potential mediator.

Diet is a potential modulator of telomere length (TL), but the impact of individual dietary components, such as nuts, on TL in young, healthy individuals remains underexplored. Peanuts are rich in bioactive compounds that may influence TL. Therefore, to fill this gap of knowledge, this study aimed to investigate the effect of peanut consumption on TL in this specific population. Fifty-eight young, healthy individuals were randomized to one of three different intervention groups for 6 months each: (1) 25 g/day of skin-roasted peanuts (SRP); (2) 32 g/day of peanut butter (PB); (3) 32 g/day of a control butter (CB) (based on peanut oil). TL was measured by quantitative real-time PCR in saliva at baseline and at the end of the intervention. Our findings revealed significant between-group differences in TL changes, particularly between the SRP and CB groups over 6 months (mean difference: 0.53; 95% CI: 0.01, 1.05; p-value = 0.048). No significant difference was observed between PB and CB groups (mean difference: 0.12; 95% CI: –0.42, 0.66; p-value = 0.66). This study provides novel insights into the impact of peanut consumption on TL maintenance in young and healthy individuals. The findings highlight the potential benefits of incorporating peanuts into the diet as a means of promoting cellular health and longevity. Further research is warranted to elucidate the underlying mechanisms and validate these findings across diverse populations and longer time frames.