Glucocorticoids trigger muscle-liver crosstalk to attenuate acute liver injury and promote liver regeneration via the FGF6-FGFBP1 axis.

Background: Acute liver injury (ALI) requires rapid hepatic regeneration to avert fatal liver failure. As key mechanisms, systemic metabolic remodeling and inter-organ crosstalk are critical for this regenerative process. Skeletal muscle, as a major metabolic organ system, undergoes significant remodeling during ALI.

E3 ligase FBXW7 suppresses brown fat expansion and browning of white fat.

Thermogenic fat, including brown and beige fat, dissipates heat via thermogenesis and enhances energy expenditure. Thus, its activation represents a therapeutic strategy to combat obesity. Here, we demonstrate that levels of F-box and WD repeat domain-containing 7 (FBXW7), an E3 ubiquitin protein ligase, negatively correlate with thermogenic fat functionality.

BMAL1/PGC1α4-FNDC5/irisin axis impacts distinct outcomes of time-of-day resistance exercise.

Background: Resistance exercise leads to improved muscle function and metabolic homeostasis. Yet how circadian rhythm impacts exercise outcomes and its molecular transduction remains elusive.

Methods: Human volunteers were subjected to 4 weeks of resistance training protocols at different times of day to assess training outcomes and their associations with myokine irisin.

FOXA3 regulates cholesterol metabolism to compensate for low uptake during the progression of lung adenocarcinoma.

Cholesterol metabolism is vital for multiple cancer progression, while how cholesterol affects lung, a low-cholesterol tissue, for cancer metastasis and the underlying mechanism remain unclear. In this study, we found that metastatic lung adenocarcinoma cells acquire cellular dehydrocholesterol and cholesterol by endogenous cholesterol biosynthesis, instead of uptake upon cholesterol treatment. Besides, we demonstrated that exogenous cholesterol functions as signaling molecule to induce FOXA3, a key transcription factor for lipid metabolism via GLI2.

Characterisation of forkhead box protein A3 as a key transcription factor for hepatocyte regeneration.

Background & Aims: Liver regeneration is vital for the recovery of liver function after injury, yet the underlying mechanism remains to be elucidated. Forkhead box protein A3 (FOXA3), a member of the forkhead box family, plays important roles in endoplasmic reticulum stress sensing, and lipid and glucose homoeostasis, yet its functions in liver regeneration are unknown.

Methods: Here, we explored whether Foxa3 regulates liver regeneration via acute and chronic liver injury mice models.

AAV-Mediated nuclear localized PGC1α4 delivery in muscle ameliorates sarcopenia and aging-associated metabolic dysfunctions.

Sarcopenia is characterized of muscle mass loss and functional decline in elder individuals which severely affects human physical activity, metabolic homeostasis, and life quality. Physical exercise is considered effective in combating muscle atrophy and sarcopenia, yet it is not feasible to elders with limited mobility. PGC-1α4, a short isoform of PGC-1α, is strongly induced in muscle under resistance training, and promotes muscle hypertrophy.

Histone deacetylase inhibitors inhibit lung adenocarcinoma metastasis via HDAC2/YY1 mediated downregulation of Cdh1.

Metastasis is a leading cause of mortality in patients with lung adenocarcinoma. Histone deacetylases have emerged as promising targets for anti-tumor drugs, with histone deacetylase inhibitors (HDACi) being an active area of research. However, the precise mechanisms by which HDACi inhibits lung cancer metastasis remain incompletely understood.

HnRNPA2B1 Aggravates Inflammation by Promoting M1 Macrophage Polarization.

Macrophages have critical contributions to both acute and chronic inflammatory diseases, for example, bowel disease and obesity, respectively. However, little is known about the post-transcriptional regulatory mechanisms in macrophage-mediated inflammatory diseases. hnRNPA2B1 (A2B1) is an RNA binding protein for mRNA fate determination.

Fibroblast Growth Factor 6 Promotes Adipocyte Progenitor Cell Proliferation for Adipose Tissue Homeostasis.

The de novo differentiation of hyperplastic adipocytes from adipocyte progenitor cells (APCs) is accompanied by a reduction in adipose tissue fibrosis and inflammation and improvement in insulin sensitivity in obesity and aging. However, the regulators of APC proliferation are poorly understood. Here, we show that fibroblast growth factor 6 (FGF6) acts in an autocrine and/or paracrine manner to control platelet-derived growth factor receptor α-positive APC proliferation via extracellular signal-regulated kinase (ERK) signaling.

Local hyperthermia therapy induces browning of white fat and treats obesity.

Beige fat plays key roles in the regulation of systemic energy homeostasis; however, detailed mechanisms and safe strategy for its activation remain elusive. In this study, we discovered that local hyperthermia therapy (LHT) targeting beige fat promoted its activation in humans and mice. LHT achieved using a hydrogel-based photothermal therapy activated beige fat, preventing and treating obesity in mice without adverse effects.

Antibiotic Azithromycin inhibits brown/beige fat functionality and promotes obesity in human and rodents.

Obesity, a metabolic disease caused by multiple factors, has become a global health problem. In addition to nutrient intake and sedentary lifestyle, environmental pollutants exposure has been shown to be involved in obesity epidemics. Antibiotics, a new type of environmental pollutant, have been widely used in animal husbandry, aquaculture and microorganism.

Combination Usage of AdipoCount and Image-Pro Plus/ImageJ Software for Quantification of Adipocyte Sizes.

In recent decades, the prevalence of obesity has been rising. One of the major characteristics of obesity is fat accumulation, including hyperplasia (increase in number) and hypertrophy (increase in size). After histological staining, it is critical to accurately measure the number and size of adipocytes for assessing the severity of obesity in a timely fashion.

FOXA3 induction under endoplasmic reticulum stress contributes to non-alcoholic fatty liver disease.

Background & Aims: Chronic endoplasmic reticulum (ER) stress in the liver has been shown to play a causative role in non-alcoholic fatty liver disease (NAFLD) progression, yet the underlying molecular mechanisms remain to be elucidated. Forkhead box A3 (FOXA3), a member of the FOX family, plays critical roles in metabolic homeostasis, although its possible functions in ER stress and fatty liver progression are unknown.

Methods: Adenoviral delivery, siRNA delivery, and genetic knockout mice were used to crease FOXA3 gain- or loss-of-function models.

N -Methyladenosine Reader Protein YT521-B Homology Domain-Containing 2 Suppresses Liver Steatosis by Regulation of mRNA Stability of Lipogenic Genes.

Background And Aims: Nonalcoholic fatty liver disease (NAFLD) is characterized by accumulation of excessive triglycerides (TGs) in hepatocytes. Obesity is a major risk factor for developing fatty liver, although the intracellular molecular basis remains largely unclear. N -methyladenosine (m A) RNA methylation is the most common internal modification in eukaryotic mRNA.

C/EBPδ-Slug-Lox1 axis promotes metastasis of lung adenocarcinoma via oxLDL uptake.

Cancer cells undergo significant lipid metabolic reprogramming to ensure sufficient energy supply for survival and progression. However, how cancer cells integrate lipid metabolic signaling with cancer progression is not well understood. In the present study, we demonstrated that C/EBPδ, a critical lipid metabolic regulator, is a TGF-β1 downstream gene and promotes lung adenocarcinoma metastasis.

Silver nanoparticles inhibit beige fat function and promote adiposity.

Objective: Obesity is a complex chronic disease of high prevalence worldwide. Multiple factors play integral roles in obesity development, with rising interest focusing on the contribution of environmental pollutants frequent in modern society. Silver nanoparticles (AgNPs) are widely used for bactericidal purpose in various applications in daily life.