Search

The regulation of adipose deposition in broiler chickens is an important factor for production efficiency to poultry producers and health concerns to customers. Although vitamin A and its metabolite [all-trans retinoic acid (atRA)] have been used for studies on adipogenesis in mammals and avian, effects of embryonic atRA on adipose development in embryonic (E) and posthatch (D) ages in broiler chickens have not been studied yet. Different concentrations of atRA (0 M–2 μM) were injected in broiler eggs at E10, and adipose tissues were sampled at E16. Percentages of adipose tissues in chicken embryos were significantly increased in the group injected with 500 nM of atRA compared to the 0 M group (P

The tumor protein D52 (TPD52) gene encodes a proto-oncogene protein associated with various medical conditions, including breast and prostate cancers. It plays a role in multiple biological pathways such as cell growth, differentiation, and apoptosis. The function of TPD52 in lipid droplet biosynthesis has been investigated in vitro. However, its precise role in lipid metabolism in animal models is not fully understood. To investigate the functions of TPD52 in vivo, we performed a conditional TPD52 protein expression analysis using a Tet-off transgenic system to establish conditionally expressed Tpd52 transgenic zebrafish. The effect of Tpd52 on lipogenesis was assessed using various methods, including whole-mount Oil Red O staining, histological examination, and measurement of inflammatory markers and potential targets using real-time quantitative polymerase chain reaction and immunoblotting in Tpd52 fish. Zebrafish with increased Tpd52 levels exhibited notable weight gain and the enlargement of fat deposits, which were mainly attributed to an increase in the volume of adipocytes. Moreover, Tpd52 overexpression was correlated with the triggering of the adipocyte differentiation signaling pathway. During adipocytic differentiation in response to nutrient status, our observations revealed adipogenesis, nonalcoholic fatty liver disease, and metabolic cardiomyopathy (MCM) in Tpd52 transgenic zebrafish. To gain a deeper understanding of the contribution of these proteins to the regulation of cellular growth, we investigated the expression of their corresponding genes and proteins in zebrafish. In the present study, the activated protein kinase pathway was identified as the primary target of TPD52. Adult Tpd52 zebrafish showed increased lipid accumulation, resulting in the development of visceral obesity, nonalcoholic fatty liver disease, and MCM. These findings strongly suggest that TPD52 actively contributes to adipose tissue expansion and its subsequent effects. This investigation provides compelling evidence that Tpd52 facilitates adipocyte development and related metabolic comorbidities in zebrafish., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Metabolic syndrome poses a great worldwide threat to the health of the patients. Increased visceral adiposity is recognized as the main determinant of the detrimental clinical effects of insulin resistance. Inflammation and immune system activation in the adipose tissue (AT) have a central role in the pathophysiology of metabolic syndrome, but the mechanisms linking increased adiposity to immunity in the AT remain in part elusive. In this review, we support the central role of adipocyte overload and relative adipose failure as key determinants in triggering immune aggression to AT. This provides a mechanistic explanation of the relative metabolic wellness of metabolically normal obese people and the disruption in insulin signaling in metabolically obese lean people., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Nobiletin is a major citrus flavonoid possessing several biological activities. Nobiletin has been reported to display anti-inflammatory activity and to reduce monocyte chemoattractant protein (MCP)-1 secretion by 3T3-L1 adipocytes. However, its mode of action remains unclear. In the present study, we investigated the suppressive effect of nobiletin on MCP-1 expression in 3T3-L1 cells and its underlying molecular mechanism. Nobiletin notably down-regulated the MCP-1 mRNA level during adipocyte differentiation. Nobiletin also reduced MCP-1 secretion by preadipocytes (undifferentiated cells), differentiated adipocytes, and hypertrophied adipocytes. Immunoblot analysis showed that nobiletin inhibits the phosphorylation level of extracellular signal-regulated kinase (ERK) in both preadipocytes and differentiated adipocytes. Moreover, nobiletin suppressed MCP-1 secretion by adipocytes induced by tumor necrosis factor (TNF)-α.

Prenatal exposure to endocrine-disrupting bisphenol A (BPA) shows a long-lasting programming effect on an organ's metabolic function and predisposes it to the risk of adult metabolic diseases. Although a reduced contaminant risk due to "BPA-free" exposure is proposed, limited data on a comparative assessment of gestational exposure to BPS and BPA and their effects on metaflammation in predisposing liver metabolic disease is reported. Pregnant Wistar rats were exposed to BPS and BPA (0.0, 0.4, 4.0 μg/kg bw) via gavage from gestational day 4 to 21, and effects were assessed in the 90 d male offspring. Prenatal BPS-exposed offspring showed a more obesogenic effect than BPA, including changes in body fat distribution, feed efficiency, and leptin signalling. The BPS exposure induced the adipocyte hypertrophy of visceral adipose to a greater extent than BPA. The adipose hypertrophy was augmented by tissue inflammation, endoplasmic reticulum (ER) stress, and apoptosis due to increased expression of pro-inflammatory (IL6, IL1β, CRP, COX2) cytokines, ER stress modulator (CHOP), and apoptotic effector (Caspase 3). The enlarged, stressed, inflamed adipocytes triggered de novo lipogenesis in the bisphenol-exposed offspring liver due to increased expression of cholesterol and lipid biogenesis mediators (srebf1, fasn, acaca, PPARα) concomitant with elevated triacylglycerol (TG) and cholesterol (TC), resulted in impaired hepatic clearance of lipids. The lipogenic effects were also promoted by increased expression of HSD11β1. BPS exposure increased absolute liver weight, discoloration, altered liver lobes more than in BPA. Liver histology showed numerous lipid droplets, and hepatocyte ballooning, upregulated ADRP expression, an increased expression of pro-inflammatory mediators (IL6, CRP, IL1β, TNFα, COX2), enhanced lipid peroxidation in the BPS-exposed offspring's liver suggest altered metaflammation leads to microvesicular steatosis. Overall, gestational BPS exposure demonstrated a higher disruption in metabolic changes than BPA, involving excess adiposity, liver fat, inflammation, and predisposition to steatosis in the adult male offspring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The regulation of adipose deposition in broiler chickens is an important factor for production efficiency to poultry producers and health concerns to customers. Although vitamin A and its metabolite [all-trans retinoic acid (atRA)] have been used for studies on adipogenesis in mammals and avian, effects of embryonic atRA on adipose development in embryonic (E) and posthatch (D) ages in broiler chickens have not been studied yet. Different concentrations of atRA (0 M-2 μM) were injected in broiler eggs at E10, and adipose tissues were sampled at E16. Percentages of adipose tissues in chicken embryos were significantly increased in the group injected with 500 nM of atRA compared to the 0 M group (P < 0.05). In addition, the adipocyte cross-sectional area (CSA) was significantly greater by in ovo injection of 500 nM atRA compared to the injection of 0 M (P < 0.01). Moreover, in ovo atRA-injected embryos were hatched and BWs were measured at D0, D7, and D14. BWs were not different from those of the 0 M group. Percentages of adipose tissues and CSA of the in ovo atRA-injected group (500 nM) were not different from those of the 0 M group at D14. Taken together, the current study clearly showed that in ovo injection of atRA promoted adipose deposition with hypertrophy during embryonic development, but its effects were not maintained in early posthatch age in broiler chickens, implying that embryonic atRA has an important role in the regulation of adipose development in chicken embryos., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Hepatic steatosis is often a consequence of obesity. Adipose tissue is an important endocrine regulator of metabolic homeostasis in the body. In obesity, adipocytes become hypertrophic and develop an inflammatory phenotype, altering the panel of secreted adipokines. Moreover, excess fatty acids are, in part, released by adipocytes and delivered to the liver. These multiple pathways of adipose-liver crosstalk contribute to the development and progression of liver disease: TNFα induces hepatocyte dysfunction, excess of circulating fatty acids promotes hepatic steatosis and inflammation, whilst adipokines mediate and exacerbate liver injury. In this study, we investigated in vitro the effects and mechanisms of the crosstalk between adipocytes and hepatocytes, as a function of the different adipocyte status (mature vs hypertrophic) being mediated by soluble factors. We employed the conditioned medium method to test how mature and hypertrophic adipocytes distinctively affect the liver, leading to metabolic dysfunction. The media collected from adipocytes were characterized by high triglyceride content and led to lipid accumulation and fat-dependent dysfunction in hepatocytes. The present findings seem to suggest that, in addition to triglycerides, other soluble mediators, cytokines, are released by mature and hypertrophic adipocytes and influence the metabolic status of liver cells. Understanding the precise factors involved in the pathogenesis and pathophysiology of NAFLD in obesity will provide important insights into the mechanisms responsible for the metabolic complications of obesity, paving the way for new possible approaches., (Copyright © 2023. Published by Elsevier Inc.)

Macrophage infiltration of white adipose tissue (WAT) is implicated in the metabolic complications of obesity. The precipitating event(s) and function(s) of macrophage infiltration into WAT are unknown. We demonstrate that >90% of all macrophages in WAT of obese mice and humans are localized to dead adipocytes, where they fuse to form syncytia that sequester and scavenge the residual “free” adipocyte lipid droplet and ultimately form multinucleate giant cells, a hallmark of chronic inflammation. Adipocyte death increases in obese (db/db) mice (30-fold) and humans and exhibits ultrastructural features of necrosis (but not apoptosis). These observations identify necrotic-like adipocyte death as a pathologic hallmark of obesity and suggest that scavenging of adipocyte debris is an important function of WAT macrophages in obese individuals. The frequency of adipocyte death is positively correlated with increased adipocyte size in obese mice and humans and in hormone-sensitive lipase-deficient (HSL−/−) mice, a model of adipocyte hypertrophy without increased adipose mass. WAT of HSL−/− mice exhibited a 15-fold increase in necrotic-like adipocyte death and formation of macrophage syncytia, coincident with increased tumor necrosis factor-α gene expression.These results provide a novel framework for understanding macrophage recruitment, function, and persistence in WAT of obese individuals.

Aims: Adipocyte hypertrophy is the main cause of obesity. A deeper understanding of the molecular mechanisms regulating adipocyte dysfunction may help to plan strategies to treat/prevent obesity and its metabolic complications. Here, we investigated in vitro the molecular alterations associated with early adipocyte hypertrophy, focusing on mitochondrial dysfunction., Main Methods: As model of adipocyte hypertrophy, we employed 3T3-L1 preadipocytes firstly differentiated into mature adipocytes, then cultured with long-chain fatty acids. As a function of differentiation and hypertrophy, we assessed triglyceride content, lipid droplet size, radical homeostasis by spectrophotometry and microscopy, as well as the expression of PPARγ, adiponectin and metallothioneins. Mitochondrial status was investigated by electron microscopy, oxygraph 2 k (O2K) high-resolution respirometry, fluorimetry and western blot., Key Findings: Compared to mature adipocytes, hypertrophic adipocytes showed increased triglyceride accumulation and lipid peroxidation, larger or unique lipid droplet, up-regulated expression of PPARγ, adiponectin and metallothioneins. At mitochondrial level, early-hypertrophic adipocytes exhibited: (i) impaired mitochondrial oxygen consumption with parallel reduction in the mitochondrial complexes; (ii) no changes in citrate synthase and HSP60 expression, and in the inner mitochondrial membrane polarization; (iii) no stimulation of mitochondrial fatty acid oxidation. Our findings indicate that the content, integrity, and catabolic activity of mitochondria were rather unchanged in early hypertrophic adipocytes, while oxygen consumption and oxidant production were altered., Significance: In the model of early adipocyte hypertrophy exacerbated oxidative stress and impaired mitochondrial respiration were observed, likely depending on reduction in the mitochondrial complexes, without changes in mitochondrial mass and integrity., (Copyright © 2020. Published by Elsevier Inc.)

Bisphenol S (BPS) has been increasingly used as a substitute for bisphenol A (BPA), a known endocrine disruptor. Early-life exposure to BPA affects fetal development and the risk of obesity in adolescence and adulthood. However, the effects of fetal exposure BPS in later life are unknown. This study aimed to investigate the effects of prenatal BPS exposure on adiposity in adult F1 mice. Pregnant C57BL/6 N mice were exposed to BPS (0, 0.05, 0.5, 5, and 50 mg/kg/d) via drinking water from gestation day 9 until delivery. Thereafter, two groups of offspring (6 weeks old) were either administered a standard diet (STD) or a high-fat diet (HFD) for 4 weeks until euthanasia. The body weight and gonadal white adipose tissue (gWAT) mass were determined, and the energy expenditure for the adiposity phenotype was computed especially for male mice, followed by histological analysis of the gWAT. Thereafter, the expression levels of adipogenic marker genes (Pparg, Cebpa, Fabp4, Lpl, and Adipoq) were analyzed in the gWAT via reverse-transcription PCR analysis. BPS-exposed male mice displayed apparent gWAT hypertrophy, consistent with the significant increase in adipocyte size in the gWAT and upregulation of Pparg and its direct target genes among HFD mice in comparison with the control mice. These results suggest that prenatal BPS exposure potentially increases the susceptibility to HFD-induced adipogenesis in male adult mice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

The gum of Gardenia resinifera Roth., is one of the important drugs used in the Indian system of medicine and a source of unique polymethoxylated flavones. This study was aimed to evaluate the antihyperlipidemic and anti-NAFLD effects of Gardenin A (Gar-A) from G. resinifera gum using in vitro and in vivo models. Gar-A was isolated from G. resinifera gum and was identified on the basis of the physical and spectral data. Toxicity of Gar-A to HepG2 cells was evaluated using MTT assay. The ability of Gar-A to reduce steatosis was assessed using oleate-palmitate induced HepG2 cell lines by estimating the lipid levels by ORO staining and by estimating the intracellular triglyceride content. Effect of Gar-A on amelioration of lipotoxicity was measured by estimating the LDH levels. The doses for in vivo experiments were fixed by Irwin test, between 50 and 100 mg/kg concentrations, through oral route. The acute antihyperlipidemic effect of Gar-A was assessed in Triton WR-1339 induced hyperlipidemic animals. The chronic antihyperlipidemic and anti-NAFLD effects of Gar-A were evaluated in HFD fed rats. In vitro experiments with HepG2 cell line indicated that the cells treated with Gar-A did not show any significant reduction in the viability up to 70 μg/mL concentration. Steatotic HepG2 cells treated with Gar-A showed a significant reduction in lipid accumulation at 2.5-10 μg/mL concentrations. In triton induced hyperlipidemic rats, the treatment significantly reduced the lipid levels at the synthesis phase. The treatment with Gar-A to the HFD fed animals significantly lowered the steatosis and transaminase levels. The other biochemical parameters such as TC, TG, LDL-c, ALP and ACP were also decreased significantly. Treatment with Gar-A significantly lowered the hyperlipidemia and fat accumulation in the liver; detailed molecular investigations are necessary to establish the antihyperlipidemic and hepatoprotective potentials of Gar-A., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The United States is a world leader in poultry production, which is the reason why achieving better performance and muscle growth each year is a necessity. Reducing accretion of adipose tissue is another important factor for poultry producers because this allows more nutrients to be directed toward muscle growth, but the effect of embryonic adipose growth on posthatch development has not been fully understood. The purpose of this study was to investigate the total DNA mass, morphological characteristics, differentiation markers, and triglyceride breakdown factors of embryonic adipose tissue, and their relation to hyperplastic and hypertrophic growth within layers (Leghorn) and meat-type chickens (broilers). After embryonic day (E) 12, broiler weight was significantly higher than Leghorn, and this trend continued throughout the rest of incubation and posthatch (P < 0.05). Neck and leg fat pad weights between the 2 breeds did not differ at most of the time points. A remarkable increase in total DNA mass was observed between E12 and E14 in both Leghorn and broilers (P < 0.05), indicating a high potential for hyperplastic growth during this time. Histological analysis revealed clusters of preadipocytes at E12; however, the majority of these cells differentiated by E14 and continued to grow until the time of hatch. The adipocyte sizes between both breeds did not generally differ, even though broilers are known to have larger adipocytes posthatch. Fatty acid-binding protein 4 expression levels in Leghorn and broilers continued to rise with each time point, which paralleled the expansion of mature adipocytes. Adipose triglyceride lipase was highly expressed at E20 and d 1 posthatch to mobilize triglyceride degradation for energy during hatching. Thus, embryonic chicken adipose tissue was found to develop by hyperplastic mechanisms followed by hypertrophy. At embryonic stages and early posthatch, layer- and meat-type chicken adipose growth does not differ, which suggests breed differences occur posthatch., (© 2014 Poultry Science Association Inc.)