This study investigates how the consumption of interesterified palm oil (IPO) affects the metabolic and morphological features of brown adipose tissue (BAT) in C57BL/6 mice fed a high-fat diet. Mice were divided into four groups: control, high-fat diet (lard), high-fat diet with palm oil (PO; HFP) and high-fat diet with IPO (HFI). The HFP and HFI groups exhibited significant body weight gain, increased fat mass and impaired glucose metabolism. Histological analyses revealed lipid infiltration in BAT, leading to structural remodelling from multilocular to unilocular adipocytes, which are hallmark features of the whitening process. This morphological shift was accompanied by reduced nuclear density and impaired vascularisation. Gene expression analysis indicated downregulation of key thermogenic markers, including Ucp1, Pparγ and Prdm16, especially in the HFI group. Increased expression of endoplasmic reticulum stress markers such as Chop and Atf4 and inflammatory cytokines (TNF-α and IL-6) highlighted the pro-inflammatory and pro-apoptotic microenvironment induced by PO and IPO. These changes culminated in a loss of BAT thermogenic capacity, as evidenced by decreased uncoupling protein 1 levels and impaired adaptive thermogenesis. Our findings underscore the detrimental effects of PO, mainly IPO, on BAT functionality, exacerbating obesity-related metabolic dysfunctions such as insulin resistance and glucose intolerance. The results emphasise the need for caution in the dietary use of these fats, particularly in ultra-processed food formulations, given their potential role in promoting adipose tissue remodelling and metabolic imbalances.

A positive association has been demonstrated between consumption of sucrose-sweetened beverages and the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD). Since the administration of 30 % sucrose in the drinking water (sucrose-rich diet (SRD)) to rats has proven to be a good model of systemic insulin resistance, the aim of our study was to analyse the effect of caloric restriction applied on SRD-treated rats by switching back to a standard diet, on liver morphology, function and metabolism. Consumption of an SRD causes a metabolic shift towards gluconeogenesis and fatty acid synthesis leading to an increase in TAG levels in plasma and in the liver that were associated with a decrease in insulin sensitivity. Moreover, our results show that animals fed an SRD develop steatohepatitis characterised by the generation of oxidative stress, endoplasmic reticulum (ER) stress, inflammation and apoptosis. Although no histological changes were observed after a 2-week caloric restriction, key pathways associated with the progression of MASLD as inflammation, ER stress and apoptosis were slowed down. Notably, this 2-week intervention also increased liver insulin sensitivity (evaluated by AKT activity in this tissue) and drove the lipid metabolic profile towards oxidation, thus lowering circulating TAG levels. In summary, the present study uncovers underlying mechanisms affected, and their metabolic consequences, during the first stages of the phenotypic reversal of steatohepatitis by switching back to a standard diet after receiving sucrose-sweetened water for several weeks.

Choline plays a crucial role in hepatic lipid homeostasis by acting as a major methyl-group donor. However, despite this well-accepted fact, no study has yet explored how choline’s methyl-donor function contributes to preventing hepatic lipid dysregulation. Moreover, the potential regulatory role of Ire-1α, an ER-transmembrane transducer for the unfolded protein response (UPRer), in choline-mediated hepatic lipid homeostasis remains unexplored. Thus, this study investigated the mechanism by which choline prevents hepatic lipid dysregulation, focusing on its role as a methyl-donor and the involvement of Ire-1α in this process. To this end, a model animal for lipid metabolism, yellow catfish (Pelteobagrus fulvidraco) were fed two different diets (adequate or deficient choline diets) in vivo for 10 weeks. The key findings of studies are as follows: 1. Dietary choline, upregulated selected lipolytic and fatty acid β-oxidation transcripts promoting hepatic lipid homeostasis. 2. Dietary choline ameliorated UPRer and prevented hepatic lipid dysregulation mainly through ire-1α signalling, not perk or atf-6α signalling. 3. Choline inhibited the transcriptional expression level of ire-1α by activating site-specific DNA methylations in the promoter of ire-1α. 4. Choline-mediated ire-1α methylations reduced Ire-1α/Fas interactions, thereby further inhibiting Fas activity and reducing lipid droplet deposition. These results offer a novel insight into the direct and indirect regulation of choline on lipid metabolism genes and suggests a potential crosstalk between ire-1α signalling and choline-deficiency-induced hepatic lipid dysregulation, highlighting the critical contribution of choline as a methyl-donor in maintaining hepatic lipid homeostasis.

Se is a micronutrient essential for human health. Sub-optimal Se status is common, occurring in a significant proportion of the population across the world including parts of Europe and China. Human and animal studies have shown that Se status is a key determinant of the host response to viral infections. In this review, we address the question whether Se intake is a factor in determining the severity of response to coronavirus disease 2019 (COVID-19). Emphasis is placed on epidemiological and animal studies which suggest that Se affects host response to RNA viruses and on the molecular mechanisms by which Se and selenoproteins modulate the inter-linked redox homeostasis, stress response and inflammatory response. Together these studies indicate that Se status is an important factor in determining the host response to viral infections. Therefore, we conclude that Se status is likely to influence human response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and that Se status is one (of several) risk factors which may impact on the outcome of SARS-CoV-2 infection, particularly in populations where Se intake is sub-optimal or low. We suggest the use of appropriate markers to assess the Se status of COVID-19 patients and possible supplementation may be beneficial in limiting the severity of symptoms, especially in countries where Se status is regarded as sub-optimal.

Ingestion of collagen peptide (CP) elicits beneficial effects on the body, including improvement in blood lipid profiles, but the underlying mechanisms remain unclear. The purpose of this study was to investigate the effects of CP ingestion on the liver, which controls lipid metabolism in the body. Male BALB/cCrSlc mice were bred with the AIN-93M diet containing 14 % casein or the AIN-93M-based low-protein diet containing 10 % casein or a diet containing 6 % casein+4 % CP for 10 weeks (n 12/group). Total, free and esterified cholesterol levels in the blood decreased in the CP group. DNA microarray analysis of the liver revealed that expressions of genes related to lipid metabolic processes such as the PPAR signalling pathway and fatty acid metabolism increased in the CP group compared with the 10 % casein group. The expressions of several genes involved in steroid metabolic process, including Cyp7a1 and Cyp8b1, were decreased, despite being targets of transcriptional regulation by PPAR. These data suggest that lipid metabolism in the liver is altered by CP ingestion, and the decrease in blood cholesterol levels in the CP group is not due to enhancement of the steroid metabolic process. On the other hand, expressions of genes related to the unfolded protein response (UPR) significantly decreased at the mRNA level, suggesting that CP ingestion lowers endoplasmic reticulum stress. Indeed, protein levels of phosphorylated inositol-requiring enzyme 1 decreased after CP ingestion. Taken together, CP affects the broader pathways in the liver – not only lipid metabolism but also UPR.

RNase L and Ire1p are members of a superfamily of regulated endoribonucleases that play essential roles in mediating diverse types of cellular stress responses. 2′-5′ oligoadenylates, produced in response to interferon treatment and viral double-stranded RNA, are necessary to activate RNase L. In contrast, unfolded proteins in the endoplasmic reticulum activate Ire1p, a transmembrane serine/threonine kinase and endoribonuclease. To probe their similarities and differences, molecular properties of wild-type and mutant forms of human RNase L and yeast Ire1p were compared. Surprisingly, RNase L and Ire1p showed mutually exclusive RNA substrate specificity and partially overlapping but not identical requirements for phylogenetically conserved amino acid residues in their nuclease domains. A functional model for RNase L was generated based on the comparative analysis with Ire1p that assigns novel roles for ankyrin repeats and kinase-like domains.