Subchondral bone marrow adipose tissue lipolysis regulates bone formation in hand osteoarthritis.

Objective: Bone marrow adipose tissue (BMAT) is emerging as an important regulator of bone formation and energy metabolism. Lipolysis of BMAT releases glycerol and fatty acid substrates that are catabolized by osteoblasts. Here, we investigated whether BMAT lipolysis is involved in subchondral bone formation in hand osteoarthritis (OA).

The influence of social media and video-on-demand platforms on the appeal and consumption of tobacco and emerging tobacco products: A cross-sectional study.

Introduction: Digital platforms serve as an avenue for the tobacco industry to promote both conventional tobacco and emerging products, with a notable focus on capturing the attention of young people through sophisticated marketing campaigns. This research aims to analyze the prevalence of different advertising strategies on digital platforms and to assess the impact of exposure to these strategies on the probability of use initiation and increased consumption of conventional tobacco and new tobacco products among young Spaniards.

Methods: An online survey was conducted on a representative sample of 1730 young Spaniards aged 16-21 years in November 2022 using a comprehensive approach, considering all possible relevant factors and perspectives regarding the issue of the study.

Systemic and joint adipose tissue lipids and their role in osteoarthritis.

Osteoarthritis (OA) is a major disease whose prevalence increases with aging, sedentary lifestyles, and obesity. The association between obesity and OA has been well documented, but the precise mechanisms underlying this heightened risk remain unclear. While obesity imposes greater forces on joints, systemic fat-derived factors such as lipids or adipokine may potentially act on the pathophysiology of OA, but the exact role of these factors in weight-bearing and non-weight-bearing joints remains elusive.

The Antiobesity Effects of Rosehip (Rosa canina) Flesh by Antagonizing the PPAR Gamma Activity in High-Fat Diet-Fed Mice.

Scope: The rosehip (Rosa canina) is a perennial shrub with a reddish pseudofruit that has demonstrated antidiabetic, antiatherosclerotic, and antiobesogenic effects in rodent models but there is low information about the molecular mechanisms underlying these effects on the onset and progression of diet-induced obesity.

Methods And Results: Four-week-old C57BL/6J male mice are subjected to a high-fat diet (HFD)-supplemented or not with R. canina flesh for 18 weeks.

FOXO1 represses PPARα-Mediated induction of FGF21 gene expression.

Fibroblast growth factor 21 (FGF21) has emerged as a metabolic regulator that exerts potent anti-diabetic and lipid-lowering effects in animal models of obesity and type 2 diabetes, showing a protective role in fatty liver disease and hepatocellular carcinoma progression. Hepatic expression of FGF21 is regulated by PPARα and is induced by fasting. Ablation of FoxO1 in liver has been shown to increase FGF21 expression in hyperglycemia.

A Mixture of Pure, Isolated Polyphenols Worsens the Insulin Resistance and Induces Kidney and Liver Fibrosis Markers in Diet-Induced Obese Mice.

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.

Lyophilized Maqui () Berry Administration Suppresses High-Fat Diet-Induced Liver Lipogenesis through the Induction of the Nuclear Corepressor SMILE.

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.

Metabolic Impact of Flavonoids Consumption in Obesity: From Central to Peripheral.

The prevention and treatment of obesity is primary based on the follow-up of a healthy lifestyle, which includes a healthy diet with an important presence of bioactive compounds such as polyphenols. For many years, the health benefits of polyphenols have been attributed to their anti-oxidant capacity as free radical scavengers. More recently it has been described that polyphenols activate other cell-signaling pathways that are not related to ROS production but rather involved in metabolic regulation.

Fibroblast Growth Factor 21 and the Adaptive Response to Nutritional Challenges.

The Fibroblast Growth Factor 21 (FGF21) is considered an attractive therapeutic target for obesity and obesity-related disorders due to its beneficial effects in lipid and carbohydrate metabolism. FGF21 response is essential under stressful conditions and its metabolic effects depend on the inducer factor or stress condition. FGF21 seems to be the key signal which communicates and coordinates the metabolic response to reverse different nutritional stresses and restores the metabolic homeostasis.

Lyophilized Maqui () Berry Induces Browning in the Subcutaneous White Adipose Tissue and Ameliorates the Insulin Resistance in High Fat Diet-Induced Obese Mice.

Maqui () berry features a unique profile of anthocyanidins that includes high amounts of delphinidin-3-O-sambubioside-5-O-glucoside and delphinidin-3-O-sambubioside and has shown positive effects on fasting glucose and insulin levels in humans and murine models of type 2 diabetes and obesity. The molecular mechanisms underlying the impact of maqui on the onset and development of the obese phenotype and insulin resistance was investigated in high fat diet-induced obese mice supplemented with a lyophilized maqui berry. Maqui-dietary supplemented animals showed better insulin response and decreased weight gain but also a differential expression of genes involved in de novo lipogenesis, fatty acid oxidation, multilocular lipid droplet formation and thermogenesis in subcutaneous white adipose tissue (scWAT).

Nutritional Regulation of Gene Expression: Carbohydrate-, Fat- and Amino Acid-Dependent Modulation of Transcriptional Activity.

The ability to detect changes in nutrient levels and generate an adequate response to these changes is essential for the proper functioning of living organisms. Adaptation to the high degree of variability in nutrient intake requires precise control of metabolic pathways. Mammals have developed different mechanisms to detect the abundance of nutrients such as sugars, lipids and amino acids and provide an integrated response.

Mediterranean Tomato-Based Sofrito Sauce Improves Fibroblast Growth Factor 21 (FGF21) Signaling in White Adipose Tissue of Obese ZUCKER Rats.

Scope: Obesity is a fibroblast growth factor 21 (FGF21)-resistant state. Since FGF21 production and signaling are regulated by some bioactive dietary compounds, we analyze the impact of Mediterranean tomato-based sofrito sauce on: (i) the FGF21 expression and signaling in visceral white adipose tissue (vWAT), and (ii) the insulin sensitivity of obese Zucker rats (OZR).

Methods And Results: OZR are fed with a sofrito-supplemented diet or control diet.

A low-protein diet induces body weight loss and browning of subcutaneous white adipose tissue through enhanced expression of hepatic fibroblast growth factor 21 (FGF21).

Scope: Fibroblast growth factor 21 (FGF21) is considered a promising therapeutic candidate for the treatment of obesity. Since FGF21 production is regulated by various nutritional factors, we analyze the impact of low protein intake on circulating levels of this growth hormone in mice and in a sub cohort of the PREDIMED (Prevención con Dieta Mediterránea) trial. We also describe the role of hepatic FGF21 in metabolic adaptation to a low-protein diet (LPD).

Nutritional regulation of fibroblast growth factor 21: from macronutrients to bioactive dietary compounds.

Obesity is a worldwide health problem mainly due to its associated comorbidities. Fibroblast growth factor 21 (FGF21) is a peptide hormone involved in metabolic homeostasis in healthy individuals and considered a promising therapeutic candidate for the treatment of obesity. FGF21 is predominantly produced by the liver but also by other tissues, such as white adipose tissue (WAT), brown adipose tissue (BAT), skeletal muscle, and pancreas in response to different stimuli such as cold and different nutritional challenges that include fasting, high-fat diets (HFDs), ketogenic diets, some amino acid-deficient diets, low protein diets, high carbohydrate diets or specific dietary bioactive compounds.

Regulation of human class I alcohol dehydrogenases by bile acids.

Class I alcohol dehydrogenases (ADH1s) are the rate-limiting enzymes for ethanol and vitamin A (retinol) metabolism in the liver. Because previous studies have shown that human ADH1 enzymes may participate in bile acid metabolism, we investigated whether the bile acid-activated nuclear receptor farnesoid X receptor (FXR) regulates ADH1 genes. In human hepatocytes, both the endogenous FXR ligand chenodeoxycholic acid and synthetic FXR-specific agonist GW4064 increased ADH1 mRNA, protein, and activity.

FGF21 mediates the lipid metabolism response to amino acid starvation.

Lipogenic gene expression in liver is repressed in mice upon leucine deprivation. The hormone fibroblast growth factor 21 (FGF21), which is critical to the adaptive metabolic response to starvation, is also induced under amino acid deprivation. Upon leucine deprivation, we found that FGF21 is needed to repress expression of lipogenic genes in liver and white adipose tissue, and stimulate phosphorylation of hormone-sensitive lipase in white adipose tissue.

Fsp27/CIDEC is a CREB target gene induced during early fasting in liver and regulated by FA oxidation rate.

FSP27 [cell death-inducing DFFA-like effector c (CIDEC) in humans] is a protein associated with lipid droplets that downregulates the fatty acid oxidation (FAO) rate when it is overexpressed. However, little is known about its physiological role in liver. Here, we show that fasting regulates liver expression of Fsp27 in a time-dependent manner.

Different fatty acid metabolism effects of (-)-epigallocatechin-3-gallate and C75 in adenocarcinoma lung cancer.

Background: Fatty acid synthase (FASN) is overexpressed and hyperactivated in several human carcinomas, including lung cancer. We characterize and compare the anti-cancer effects of the FASN inhibitors C75 and (-)-epigallocatechin-3-gallate (EGCG) in a lung cancer model.

Methods: We evaluated in vitro the effects of C75 and EGCG on fatty acid metabolism (FASN and CPT enzymes), cellular proliferation, apoptosis and cell signaling (EGFR, ERK1/2, AKT and mTOR) in human A549 lung carcinoma cells.

PGC-1β regulates mouse carnitine-acylcarnitine translocase through estrogen-related receptor α.

Carnitine/acylcarnitine translocase (CACT) is a mitochondrial-membrane carrier proteins that mediates the transport of acylcarnitines into the mitochondrial matrix for their oxidation by the mitochondrial fatty acid-oxidation pathway. CACT deficiency causes a variety of pathological conditions, such as hypoketotic hypoglycemia, cardiac arrest, hepatomegaly, hepatic dysfunction and muscle weakness, and it can be fatal in newborns and infants. Here we report that expression of the Cact gene is induced in mouse skeletal muscle after 24h of fasting.

New synthetic inhibitors of fatty acid synthase with anticancer activity.

Fatty acid synthase (FASN) is a lipogenic enzyme that is highly expressed in different human cancers. Here we report the development of a new series of polyphenolic compounds 5-30 that have been evaluated for their cytotoxic capacity in SK-Br3 cells, a human breast cancer cell line with high FASN expression. The compounds with an IC(50) < 50 μM have been tested for their ability to inhibit FASN activity.

Activating transcription factor 4-dependent induction of FGF21 during amino acid deprivation.

Nutrient deprivation or starvation frequently correlates with amino acid limitation. Amino acid starvation initiates a signal transduction cascade starting with the activation of the kinase GCN2 (general control non-derepressible 2) phosphorylation of eIF2 (eukaryotic initiation factor 2), global protein synthesis reduction and increased ATF4 (activating transcription factor 4). ATF4 modulates a wide spectrum of genes involved in the adaptation to dietary stress.

Human HMGCS2 regulates mitochondrial fatty acid oxidation and FGF21 expression in HepG2 cell line.

HMGCS2 (hydroxymethylglutaryl CoA synthase 2), the gene that regulates ketone body production, is barely expressed in cultured cell lines. In this study, we restored HMGCS2 expression and activity in HepG2 cells, thus showing that the wild type enzyme can induce fatty acid β-oxidation (FAO) and ketogenesis, whereas a catalytically inactive mutant C166A did not generate either process. Peroxisome proliferator-activated receptor (PPAR) α expression also induces fatty acid β-oxidation and endogenous HMGCS2 expression.

Transcriptional regulation of the human acetoacetyl-CoA synthetase gene by PPARgamma.

In the cytosol of lipogenic tissue, ketone bodies are activated by AACS (acetoacetyl-CoA synthetase) and incorporated into cholesterol and fatty acids. AACS gene expression is particularly abundant in white adipose tissue, as it is induced during adipocyte differentiation. In order to elucidate the mechanism controlling the gene expression of human AACS and to clarify its physiological role, we isolated the human promoter, characterized the elements required to initiate transcription and analysed the expression of the gene in response to PPARgamma (peroxisome-proliferator-activated receptor gamma), an inducer of adipogenesis.

Novel Inhibitors of Fatty Acid Synthase with Anticancer Activity.

PURPOSE: Fatty acid synthase (FASN) is overexpressed in human breast carcinoma. The natural polyphenol (-)-epigallocatechin-3-gallate blocks in vitro FASN activity and leads to apoptosis in breast cancer cells without any effects on carnitine palmitoyltransferase-1 (CPT-1) activity, and in vivo, does not decrease body weight. We synthesized a panel of new polyphenolic compounds and tested their effects on breast cancer models.