Zebrafish obesity

Food intake and energy balance are tightly regulated by a group of hypothalamic arcuate neurons expressing the proopiomelanocortin ( POMC) gene. In mammals, arcuate-specific POMC expression is driven by two cis -acting transcriptional enhancers known as nPE1 and nPE2. Because mutant mice lacking these two enhancers still showed hypothalamic Pomc mRNA, we searched for additional elements contributing to arcuate Pomc expression. By combining molecular evolution with reporter gene expression in transgenic zebrafish and mice, here, we identified a mammalian arcuate-specific Pomc enhancer that we named nPE3, carrying several binding sites also present in nPE1 and nPE2 for transcription factors known to activate neuronal Pomc expression, such as ISL1, NKX2...

Obesity is a public health concern resulting in a variety of health complications, including heart disease and insulin resistance. Estrogens have been associated with a reduced risk of obesity, but this relationship remains incompletely understood. We assessed the role of 17β-estradiol (E2) in mitigating complications associated with obesity by supplementing E2 in the diets of overfed zebrafish. We report that dietary E2 supplementation protects against weight gain and modulates de novo cholesterol synthesis in a sex-specific manner...

BACKGROUND: Obesity, defined as excessive or abnormal body fat accumulation, which could significantly increase the risk of cardiovascular disease, type 2 diabetes mellitus (T2DM) diseases and seriously affect people's quality of life. More than 2 billion people are overweight, and the incidence of obesity is increasing rapidly worldwide, it has become a widely concerned public health issue in the world. Diverse evidence show that active metabolites are involved in the pathophysiological processes of obesity...

Cold-induced injuries severely limit opportunities and outcomes of hypothermic therapies and organ preservation, calling for better understanding of cold adaptation. Here, by surveying cold-altered chromatin accessibility and integrated CUT&Tag/RNA-seq analyses in human stem cells, we reveal forkhead box O1 (FOXO1) as a key transcription factor for autonomous cold adaptation. Accordingly, we find a nonconventional, temperature-sensitive FOXO1 transport mechanism involving the nuclear pore complex protein RANBP2, SUMO-modification of transporter proteins Importin-7 and Exportin-1, and a SUMO-interacting motif on FOXO1...

The zebrafish ( Danio rerio ) has emerged as an appreciated and versatile model organism for studying cardiovascular and metabolic diseases, offering unique advantages for both basic research and drug discovery. The genetic conservation between zebrafish and humans and their high fecundity and transparent embryos allow for efficient large-scale genetic and drug-oriented screening studies. Zebrafish possess a simplified cardiovascular system that shares similarities with mammals, making them particularly suitable for modeling various aspects of heart development, function, and disease...

Type 2 diabetes (T2D) has become a worldwide epidemic, primarily driven by obesity from overnutrition and sedentariness. Recent results reveal there is heterogeneity in both pathology and treatment responses in T2D patients. Therefore, a variety of T2D animal models are necessary to obtain a mechanistic understanding of distinct disease processes. T2D results from insufficient insulin, either due to beta cell loss or inborn deficiency. Although decreases in beta cell mass can occur through loss of identity or cell death, in this review, we will highlight the T2D animal models that display beta cell death, including the Zucker Diabetic Fatty Rat, sand rat, db/db mouse, and a novel diabetic zebrafish model, the Zebrafish Muscle Insulin-Resistant (zMIR) fish...

Epicardial adipose tissue (eAT) is a metabolically active fat depot that has been associated with a wide array of cardiac homeostatic functions and cardiometabolic diseases. A full understanding of its diverse physiological and pathological roles is hindered by the dearth of animal models. Here, we show, in the heart of an ectothermic teleost, the zebrafish, the existence of a fat depot localized underneath the epicardium, originating from the epicardium and exhibiting the molecular signature of beige adipocytes...

Understanding adipose metabolism is essential for addressing obesity and related health concerns. However, the ethical and scientific pressure to animal testing, aligning with the 3Rs, has triggered the implementation of diverse alternative models for analysing anomalies in adipose metabolism. In this review, we will address this issue from various perspectives. Traditional adipocyte cell cultures, whether animal or human-derived, offer a fundamental starting point. These systems have their merits but may not fully replicate in vivo complexity...

Exposure of zebrafish embryos to glucose is a suitable model for the fetal hyperglycemia seen in gestational diabetes. Diethylhexyl phthalate (DEHP), which is considered an endocrine-disrupting chemical, is one of the most common phthalate derivatives used in stretching plastic and is encountered in every area where plastic is used in daily life. In the present study, the effects of DEHP on pathways related to insulin resistance and obesity were examined in zebrafish embryos exposed to glucose as a fetal hyperglycemia model...

Alpha lipoic acid (ALA) is a dietary supplement that has been used to treat a wide range of diseases including obesity and diabetes and have lipid-lowering effects, making it a potential candidate for mitigating dyslipidemia resulting from exposures to the per- and polyfluoroalkyl substance (PFAS) family member perfluorooctanesulfonic acid (PFOS). ALA can be considered a non-fluorinated structural analog to PFOS due to their similar 8-carbon chain and amphipathic structure, but, unlike PFOS, is rapidly metabolized...

Zebrafish have been utilized for many years as a model animal for pharmacological studies on diabetes and obesity. High-fat diet (HFD), streptozotocin and alloxan injection, and glucose immersion have all been used to induce diabetes and obesity in zebrafish. Currently, studies commonly used both male and female zebrafish, which may influence the outcomes since male and female zebrafish are biologically different. This study was designed to investigate the difference between the metabolites of male and female diabetic zebrafish, using limonene - a natural product which has shown several promising results in vitro and in vivo in treating diabetes and obesity-and provide new insights into how endogenous metabolites change following limonene treatment...

BACKGROUND: Bacterial-sourced single-cell proteins (SCPs) offer an alternative protein source for diet formulation for Zebrafish ( Danio rerio) and other aquaculture models. In addition, the use of a single-cell bacterial protein source derived from multiple species provides a unique insight into the interplay among nutrients in the diet, microbial populations in the diet, and the gut microbiome in D. rerio . OBJECTIVE: Our objective in this study was to evaluate the impact of dietary replacement of fish protein hydrolysate in a standard reference (SR) with a single-cell bacterial protein source on D...

Obesity is a complex chronic condition associated with multiple health risks, including visceral obesity, which is particularly detrimental. To gain insight into the mechanisms underlying obesity and its associated pathologies, a novel zebrafish model was established using an innovative high-fat diet (HFD). The primary goal was to induce visceral obesity in zebrafish and study the associated structural changes. To achieve this, a unique HFD consisting of 40% beef fat (HFD40) was developed and supplemented with magnesium aluminometasilicate to improve stability in a high humidity environment...

Diabetic retinopathy (DR) is a leading cause of irreversible vision loss in working-age populations. Fat mass and obesity-associated protein (FTO) is an N6 -methyladenosine (m6 A) demethylase that demethylates RNAs involved in energy homeostasis, though its influence on DR is not well studied. Herein, we detected elevated FTO expression in vitreous fibrovascular membranes of patients with proliferative DR. FTO promoted cell cycle progression and tip cell formation of endothelial cells (ECs) to facilitate angiogenesis in vitro, in mice, and in zebrafish...

Obesity and overweight, frequently caused by a lack of exercise, are associated with many metabolic diseases, such as hypertension, diabetes, and dyslipidemia. Aerobic exercise effectively increases the high-density lipoproteins-cholesterol (HDL-C) levels and alleviates the triglyceride (TG) levels. The consumption of Cuban policosanol (Raydel® ) is also effective in enhancing the HDL-C quantity and HDL functionality to treat dyslipidemia and hypertension. On the other hand, no study has examined the effects of a combination of high-intensity exercise and policosanol consumption in obese subjects to improve metabolic disorders...

Ozonated sunflower oil (OSO) is renowned for its diverse therapeutic benefits. Nonetheless, the consequences of extended dietary intake of OSO have yet to be thoroughly investigated. Herein, the effect of 2-year dietary supplementation of OSO was examined on the survivability, obesity, skeletal deformities, swimming behavior, and liver, kidney, ovary, and testis function of zebrafish. Results showed that the zebrafish feed supplemented with 20% ( wt / wt ) OSO for 2 years emerged with higher survivability and body weight management compared to sunflower oil (SO) and normal diet (ND)-supplemented zebrafish...

BACKGROUND: Effective use of Danio rerio as a preclinical model requires standardization of macronutrient sources to achieve scientific reproducibility across studies and labs. OBJECTIVE: Our objective was to evaluate a bacterial-based single-cell protein (SCP) for the production of open-source standardized diets with defined health characteristics for the zebrafish research community. METHODS: We completed a 16-wk feeding trial using juvenile D...

Persistent organic pollutants (POPs) are toxic chemicals that can accumulate in the human body, and particularly in adipose tissue. POPs can induce metabolic diseases via mitochondrial dysfunction and can also cause cancer, obesity, and cardiovascular and neurodegenerative diseases. Although the effects of POPs were studied by evaluating mitochondrial function, which is fundamental in investigating the etiologies of various metabolic diseases, the physiological impact of POPs released by the decomposition of fat in adipose tissue is barely understood...

Obesity is an emerging global health issue with an increasing risk of disease linked to lifestyle choices. Previously, we reported that the hexane extract of Citrus sphaerocarpa (CSHE) suppressed lipid accumulation in differentiated 3T3-L1 adipocytes. In this study, we conducted in vivo experiments to assess whether CSHE suppressed obesity in zebrafish and mouse models. We administered 10 and 20 μg/mL CSHE to obese zebrafish juveniles. CSHE significantly inhibited visceral fat accumulation compared to untreated obese fish...

As a potential environmental obesogen, triclosan (TCS) carries inherent risks of inducing obesity and metabolic disorders. However, the underlying molecular mechanisms behind the lipid metabolism disorder induced by TCS have remained elusive. Through a fusion of transcriptomics and microRNA target prediction, we hypothesize that miR-101a as a responsive miRNA to TCS exposure in zebrafish, playing a central role in disturbing lipid homeostasis. As an evidence, TCS exposure triggers a reduction in miR-10a expression that accompanied by elevation of genes linked to regulation of lipid homeostasis...