Prenatal Choline Supplementation Improves Glucose Tolerance and Reduces Liver Fat Accumulation in Mouse Offspring Exposed to Ethanol during the Prenatal and Postnatal Periods.

Prenatal alcohol exposure (AE) affects cognitive development. However, it is unclear whether prenatal AE influences the metabolic health of offspring and whether postnatal AE exacerbates metabolic deterioration resulting from prenatal AE. Choline is a semi-essential nutrient that has been demonstrated to mitigate the cognitive impairment of prenatal AE.

Retinoic Acid Receptor β Loss in Hepatocytes Increases Steatosis and Elevates the Integrated Stress Response in Alcohol-Associated Liver Disease.

In alcohol-associated liver disease (ALD), hepatic reductions in vitamin A and perturbations in vitamin A metabolism are common. However, the roles that the vitamin A receptors, termed retinoic acid receptors (RARs), may have in preventing the pathophysiology of ALD remains unclear. Our prior data indicate that a RARβ agonist limits the pathology of alcohol-related liver disease.

Fenretinide Reduces Intestinal Mucin-2-Positive Goblet Cells in Chronic Alcohol Abuse.

Introduction: Alcohol-induced thickening of the gut mucosal layer and increased expression of goblet cell gel-forming mucins, such as mucin-2 (MUC2) are associated with disruptions to the gut barrier in alcoholic liver disease (ALD). Interest in drugs that can target gut mucins in ALD has grown; however to date, no studies have examined the properties of drugs on expression of gut mucins in models of ALD. We previously demonstrated that at 10 mg/kg/day, the drug fenretinide (N-[4-hydroxyphenyl] retinamide [Fen]), a synthetic retinoid, mitigates alcohol-associated damage to the gut barrier and liver injury in a murine model of ALD.

Retinoids in the Pathogenesis and Treatment of Liver Diseases.

Vitamin A (VA), all-trans-retinol (ROL), and its analogs are collectively called retinoids. Acting through the retinoic acid receptors RARα, RARβ, and RARγ, all-trans-retinoic acid, an active metabolite of VA, is a potent regulator of numerous biological pathways, including embryonic and somatic cellular differentiation, immune functions, and energy metabolism. The liver is the primary organ for retinoid storage and metabolism in humans.

Maternal Choline Supplementation and High-Fat Feeding Interact to Influence DNA Methylation in Offspring in a Time-Specific Manner.

Maternal methyl donor supplementation during pregnancy has demonstrated lasting influence on offspring DNA methylation. However, it is unknown whether an adverse postnatal environment, such as high-fat (HF) feeding, overrides the influence of prenatal methyl donor supplementation on offspring epigenome. In this study, we examined whether maternal supplementation of choline (CS), a methyl donor, interacts with prenatal and postnatal HF feeding to alter global and site-specific DNA methylation in offspring.

mTOR1c Activation with the Leucine "Trigger" for Prevention of Sarcopenia in Older Adults During Lockdown.

Sarcopenia and muscle wasting have many negative impacts on health and well-being. Evidence suggests that high rates of COVID-19 hospitalizations and lockdown conditions will lead to a marked increase in musculoskeletal disorders associated with sarcopenia in older adults. The molecular etiology of sarcopenia is complex, but physical inactivity, poor diet, and age diminished ability to stimulate muscle protein synthesis (MPS) remain important drivers.

A retinoic acid receptor β2 agonist protects against alcohol liver disease and modulates hepatic expression of canonical retinoid metabolism genes.

Alcohol abuse reduces hepatic vitamin A (retinoids), reductions that are associated with progression of alcohol liver disease (ALD). Restoring hepatic retinoids through diet is contraindicated in ALD due to the negative effects of alcohol on retinoid metabolism. There are currently no drugs that can both mitigate alcohol-driven hepatic retinoid losses and progression of ALD.

Success and failures of telehealth during COVID-19 should inform digital applications to combat obesity.

Background: In response to the COVID-19 pandemic, telehealth digital applications (apps) permitted the delivery of health care to millions of individuals, including those with poor access to health services.

Aim: To review a body of evidence demonstrating that telehealth and mobile health (mHealth) apps can promote clinically meaningful weight loss, and thus hold potential to increase access to treatment and weight loss care for individuals suffering from obesity.

Results: Data from COVID-19 pandemic revealed that access to telehealth and mHealth remains a challenge for underserved communities that are disproportionately affected by obesity.

Remission of Type 2 Diabetes with Very Low-Calorie Diets-A Narrative Review.

Very low-calorie diets (VLCD) are hypocaloric dietary regimens of approximately 400-800 kcal/day that result in 20-30% reductions in body weight, sometimes in just 12-16 weeks. A body of evidence demonstrates that adherence to VLCD in adults with type 2 diabetes (T2D) can result in marked improvements to glycemic control and even full T2D remission, challenging the convention that T2D is a lifelong disease. Although these data are promising, the majority of VLCD studies have focused on weight loss and not T2D remission as a primary endpoint.

Fenretinide Improves Intestinal Barrier Function and Mitigates Alcohol Liver Disease.

Alcohol liver disease (ALD) is a major cause of liver-related mortality globally, yet there remains an unmet demand for approved ALD drugs. The pathogenesis of ALD involves perturbations to the intestinal barrier and subsequent translocation of bacterial endotoxin that, acting through toll-like receptor 4 (TLR4), promotes hepatic inflammation and progression of ALD. In the present study we investigated the ability of fenretinide (Fen) [N-(4-hydroxyphenyl) retinamide], a synthetic retinoid with known anti-cancer and anti-inflammatory properties, to modulate intestinal permeability and clinical hallmarks of ALD in a mouse model of chronic ethanol (EtOH) exposure.

A role for retinoids in the treatment of COVID-19?

The 2020 global outbreak of the novel coronavirus (SARS-CoV-2 or COVID-19) is a serious threat to international health, and thus, there is an urgent need for discovery of novel therapies or use of repurposed drugs that can make a significant impact on slowing the spread of the virus. Type 1 interferons (IFN-I) are a family cytokines of the early innate immune response to viruses that are being tested against SARS-CoV-2. However, coronaviruses similar to SARS-CoV-2 can suppress host IFN-I antiviral responses.

Effects of AM80 compared to AC261066 in a high fat diet mouse model of liver disease.

The roles of retinoids in nonalcoholic fatty liver disease (NAFLD) remain unclear and a better understanding may lead to therapies that prevent or limit NAFLD progression. We examined the actions of retinoic acid receptor (RAR) agonists- AM80 for RARα and AC261066 for RARβ2- in a murine model of NAFLD. We fed wild type C57Bl/6 mice a chow or a 45% high fat diet (HFD) for 12 weeks, followed by 4 additional weeks with the HFD+AM80; HFD+AC261066; or HFD.

Amelioration of Diabetic Nephropathy Using a Retinoic Acid Receptor 2 Agonist.

Vitamin A (VA) and its derivatives, known as retinoids, play critical roles in renal development through retinoic acid receptor 2 (RAR2). Disruptions in VA signaling pathways are associated with the onset of diabetic nephropathy (DN). Despite the known role of RAR2 in renal development, the effects of selective agonists for RAR2 in a high-fat diet (HFD) model of DN are unknown.

A retinoic acid receptor β2 agonist reduces hepatic stellate cell activation in nonalcoholic fatty liver disease.

Unlabelled: Hepatic stellate cells (HSCs) are an important cellular target for the development of novel pharmacological therapies to prevent and treat nonalcoholic fatty liver diseases (NAFLD). Using a high fat diet (HFD) model of NAFLD, we sought to determine if synthetic selective agonists for retinoic acid receptor β2 (RARβ2) and RARγ can mitigate HSC activation and HSC relevant signaling pathways during early stages of NAFLD, before the onset of liver injury. We demonstrate that the highly selective RARβ2 agonist, AC261066, can reduce the activation of HSCs, marked by decreased HSC expression of α-smooth muscle actin (α-SMA), in mice with HFD-induced NAFLD.

Vitamin A: a missing link in diabetes?

Vitamin A has a critical role in embryonic development, immunity and the visual cycle. In recent years, evidence has demonstrated that vitamin A can also regulate metabolic pathways implicated in the pathogenesis of obesity and diabetes. This has increased interest in the possible antiobesity and antidiabetic properties of natural and synthetic vitamin A derivatives.

Obesity Leads to Tissue, but not Serum Vitamin A Deficiency.

Obesity negatively affects multiple metabolic pathways, but little is known about the impact of obesity on vitamin A (VA)[retinol (ROL)], a nutrient that regulates expression of genes in numerous pathways essential for human development and health. We demonstrate that obese mice, generated from a high fat diet (HFD) or by genetic mutations (i.e.

Vitamin A deficiency causes hyperglycemia and loss of pancreatic β-cell mass.

We show that vitamin A (all-trans-retinol) (VA) is required both for the maintenance of pancreatic β-cell and α-cell mass and for glucose-stimulated insulin secretion in adult mice. Dietary VA deprivation (VAD) causes greatly decreased pancreatic VA levels, hyperglycemia, and reduced insulin secretion. Adult mice fed VAD diets display remodeling of the endocrine pancreas, marked β-cell apoptosis, shifts to smaller islet size distributions, decreased β-cell mass, increased α-cell mass, and hyperglucagonemia.

Feeding probiotic Lactobacillus paracasei to Ossabaw pigs on a high-fat diet prevents cholesteryl-ester accumulation and LPS modulation of the Liver X receptor and inflammatory axis in alveolar macrophages.

Liver X receptors (LXR) play an integral role in cholesterol metabolism and the inflammatory response. High-fat (HF) diets and microbial infection can antagonize the LXR pathway leading to accumulation of cholesteryl-esters (CE) and increased expression of pro-inflammatory mediators in macrophages. The probiotic bacteria Lactobacillus paracasei possesses cholesterol lowering and immune modulating properties.

Ligand, receptor, and cell type-dependent regulation of ABCA1 and ABCG1 mRNA in prostate cancer epithelial cells.

Recent evidence suggests that the liver X receptor (LXR) is a potential anticancer target in prostate carcinoma. There is little characterization, however, of which of the two LXR isoforms, LXRalpha or LXRbeta, regulates the LXR-responsive genes ATP-binding cassette subfamily members A1 (ABCA1) and G1 (ABCG1) in transformed prostatic epithelial cells. In this study, small interfering RNA (siRNA) was used to determine whether LXRalpha or LXRbeta is involved in regulating ABCA1 and ABCG1 mRNA expression in LNCaP and PC-3 cells.

Prolonged decrease of adipocyte size after rosiglitazone treatment in high- and low-fat-fed rats.

Objective: The anti-diabetic thiazolidinediones (TZDs) stimulate adipocyte differentiation and decrease mean adipocyte size. However, whether these smaller, more insulin-sensitive adipocytes maintain their size after TZD therapy is discontinued has not been studied.

Research Methods And Procedures: Adult female Sprague-Dawley rats were fed a low-fat (10% fat) diet or, to elevate body weight (BW), a high-fat (HF) diet (45% fat) for 6 weeks.

Androgen regulation of aldehyde dehydrogenase 1A3 (ALDH1A3) in the androgen-responsive human prostate cancer cell line LNCaP.

Previous gene array data from our laboratory identified the retinoic acid (RA) biosynthesis enzyme aldehyde dehydrogenase 1A3 (ALDH1A3) as a putative androgen-responsive gene in human prostate cancer epithelial (LNCaP) cells. In the present study, we attempted to identify if any of the three ALDH1A/RA synthesis enzymes are androgen responsive and how this may affect retinoid-mediated effects in LNCaP cells. We demonstrated that exposure of LNCaP cells to the androgen dihydrotestosterone (DHT) results in a 4-fold increase in ALDH1A3 mRNA levels compared with the untreated control.