Adipocytes In White Adipose Tissue Research Articles

Morphological Evaluation and Immunohistochemical Analysis of the Reparative Potential of the Buccal Fat Pad.

Background and Objectives: There are many surgical techniques for oroantral communication treatment, one of which is the buccal fat pad. Of particular interest is the high reparative potential of the buccal fat pad, which may be contributed to by the presence of mesenchymal stem cells. The purpose of this work is to evaluate the reparative potential of BFP cells using morphological and immunohistochemical examination. Materials and Methods: 30 BFP samples were provided by the Clinic of Maxillofacial and Plastic Surgery of the Russian University of Medicine (Moscow, Russia) from 28 patients. Morphological examination of 30 BFP samples was performed at the Institute of Clinical Morphology and Digital Pathology of Sechenov University. Hematoxylin-eosin, Masson trichrome staining and immunohistochemical examination were performed to detect MSCs using primary antibodies CD133, CD44 and CD10. Results: During staining with hematoxylin-eosin and Masson's trichrome, we detected adipocytes of white adipose tissue united into lobules separated by connective tissue layers, a large number of vessels of different calibers, as well as the general capsule of BFP. The thin connective tissue layers contained neurovascular bundles. Statistical processing of the results of the IHC examination of the samples using the Mann-Whitney criterion revealed that the total number of samples in which the expression of CD44, CD10 and CD133 antigens was confirmed was statistically significantly higher than the number of samples where the expression was not detected (p < 0.05). Conclusions: During the morphological study of the BFP samples, we revealed statistically significant signs of MSCs presence (p < 0.05), including in the brown fat tissue, which proves the high reparative potential of this type of tissue and can make the BFP a choice option among other autogenous donor materials when eliminating OAC and other surgical interventions in the maxillofacial region.

Nanomodulator-Mediated Restructuring of Adipose Tissue Immune Microenvironments for Antiobesity Treatment.

In obesity, the interactions between proinflammatory macrophages and adipocytes in white adipose tissues are known to play a crucial role in disease progression by providing inflammatory microenvironments. Here, we report that the functional nanoparticle-mediated modulation of crosstalk between adipocytes and macrophages can remodel adipocyte immune microenvironments. As a functional nanomodulator, we designed antivascular cell adhesion molecule (VCAM)-1 antibody-conjugated and amlexanox-loaded polydopamine nanoparticles (VAPN). Amlexanox was used as a model drug to increase energy expenditure. Compared to nanoparticles lacking antibody modification or amlexanox, VAPN showed significantly greater binding to VCAM-1-expressing adipocytes and lowered the interaction of adipocytes with macrophages. In high fat diet-fed mice, repeated subcutaneous administration of VAPN increased the populations of beige adipocytes and ameliorated inflammation in white adipose tissues. Moreover, the localized application of VAPN in vivo exerted a systemic metabolic effect and reduced metabolic disorders, including insulin tolerance and liver steatosis. These findings suggested that VAPN had potential to modulate the immune microenvironments of adipose tissues for the immunologic treatment of obesity. Although we used amlexanox as a model drug and anti-VCAM-1 antibody in VAPN, the concept of immune nanomodulators can be widely applied to the immunological treatment of obesity.

Protein PRDM16 and its importance for adipose tissue (literature review)

Currently, in Russia and in the world, there is an increase in the proportion of overweight and obese people among the population, which contributes to an increase in the number of socially significant diseases. Obesity is associated with the predominance of the proportion of fat mass in the component composition of the body. Based on this, increased attention is paid to a comprehensive study of the functioning of all types of human adipose tissue, which is necessary for the further use of this knowledge in the fight against obesity. This article provides an overview of the literature data on the structure and properties of the PRDM16 gene, the features of its functioning in brown, white and beige adipose tissue. The influence of the PRDM16 gene on the activation of brown adipogenesis and the formation of beige adipocytes in white adipose tissue, which contribute to increased heat production of cells by means of non-contractile thermogenesis and improvement of metabolic parameters of the body, is considered. Data on the role of PRDM16 protein in the treatment of obesity, type 2 diabetes mellitus and other human diseases associated with it are analyzed. The results on the methods of effective activation of brown and beige adipocytes and the use of these methods in the treatment of obesity are presented.

Cognitive Performance during the Development of Diabetes in the Zucker Diabetic Fatty Rat.

Increased insulin levels may support the development of neural circuits involved in cognition, while chronic mild inflammation may also result in cognitive impairment. This study aimed to gain more insight into whether cognition is already impacted during adolescence in a genetic rat model for obesity and type 2 diabetes. Visual discrimination learning throughout adolescence and the level of motivation during early adulthood were investigated in Zucker Diabetic Fatty (ZDF) obese and ZDF lean rats using operant touchscreens. Blood glucose, insulin, and lipids were longitudinally analyzed. Histological analyses were performed in the liver, white adipose tissues, and the prefrontal cortex. Prior to the experiments with the genetic ZDF research model, all experimental assays were performed in two groups of outbred Long Evans rats to investigate the effect of different feeding circumstances. Adolescent ZDF obese rats outperformed ZDF lean rats on visual discrimination performance. During the longitudinal cognitive testing period, insulin levels sharply increased over weeks in ZDF obese rats and were significantly enhanced from 6 weeks of age onwards. Early signs of liver steatosis and enlarged adipocytes in white adipose tissue were observed in early adult ZDF obese rats. Histological analyses in early adulthood showed no group differences in the number of prefrontal cortex neurons and microglia, nor PSD95 and SIRT1 mRNA expression levels. Together, our data show that adolescent ZDF obese rats even display enhanced cognition despite their early diabetic profile.

The ketogenic diet promotes triacylglycerol recycling in white adipose tissue and uncoupled fat oxidation in brown adipose tissue, but does not reduce adiposity in rats

The purpose of this study was to determine whether the weight-reducing and fat burning effects of the ketogenic diet (KD) could be attributed to alterations in the energy dissipating pathways of brown adipose tissue (BAT) uncoupled oxidation, and white adipose tissue (WAT) browning and triacylglycerol (TAG) recycling. To investigate this, male Wistar rats were fed one of the following three diets for either 8 or 16 weeks: a standard chow (SC), a high-fat, sucrose-enriched (HFS) obesogenic diet, or a KD. At the end of the intervention, subcutaneous inguinal (Sc Ing) and epididymal (Epid) fat, and interscapular and aortic BAT (iBAT and aBAT, respectively) were extracted. These tissues were used for the analysis of proteins involved in WAT browning and thermogenesis. Isolated adipocytes from WAT were assayed for basal and isoproterenol (Iso)-stimulated lipolysis and basal and insulin-stimulated lipogenesis, and BAT adipocytes were assayed for the determination of coupled and uncoupled glucose and palmitate oxidation. Adiposity similarly increased in HFS- and KD-fed rats at weeks 8 and 16. However, in HFS-fed animals insulin-stimulated lipogenesis and Iso-stimulated lipolysis were impaired in WAT adipocytes, whereas in KD-fed animals these pathways remained intact. The KD also significantly elevated WAT glycerol kinase levels, and favored TAG recycling under conditions of enhanced lipolysis. In BAT, the KD significantly increased uncoupling protein-1 levels and uncoupled fat oxidation. In summary, the KD preserved insulin sensitivity and lipolytic capacity in WAT and also upregulated energy-dissipating pathways in BAT, but it was not sufficient to prevent an increase in adiposity.

Activation of METTL3 promotes white adipose tissue beiging and combats obesity.

The induction of beige adipocytes in white adipose tissue, also known as WAT beiging, improves glucose and lipid metabolism. However, the regulation of WAT beiging at the posttranscriptional level remains to be studied. Here, we report that METTL3, the methyltransferase of N6-methyladenosine (m6A) mRNA modification, is induced during WAT beiging in mice. Adipose-specific depletion of Mettl3 gene undermines WAT beiging and impairs the metabolic capability of mice fed with a high-fat diet (HFD). Mechanistically, METTL3-catalyzed m6A installation on thermogenic mRNAs, including Krüppel-like factor 9 (Klf9), prevents their degradation. Activation of METTL3 complex by its chemical ligand methyl piperidine-3-carboxylate promotes WAT beiging, reduces body weight, and corrects metabolic disorders in diet-induced obese mice. These findings uncover a novel epitranscriptional mechanism in WAT beiging and identify METTL3 as a potential therapeutic target for obesity-associated diseases.

Semi-Automated Isolation of the Stromal Vascular Fraction from Murine White Adipose Tissue Using a Tissue Dissociator.

The in vitro study of white, brown, and beige adipocyte differentiation enables the investigation of cell-autonomous functions of adipocytes and their mechanisms. Immortalized white preadipocyte cell lines are publicly available and widely used. However, the emergence of beige adipocytes in white adipose tissue in response to external cues is difficult to recapitulate to the full extent using publicly available white adipocyte cell lines. Isolation of the stromal vascular fraction (SVF) from murine adipose tissue is commonly executed to obtain primary preadipocytes and perform adipocyte differentiation. However, mincing and collagenase digestion of adipose tissue by hand can result in experimental variation and is prone to contamination. Here, we present a modified semi-automated protocol that utilizes a tissue dissociator for collagenase digestion to achieve easier isolation of the SVF, with the aim of reducing experimental variation, reducing contamination, and increasing reproducibility. The obtained preadipocytes and differentiated adipocytes can be used for functional and mechanistic analyses.

Fibroblast growth factor 21 as a new tool in the multicomponent assessment of cardiovascular diseases

Currently, the search and study of new biological markers that can assist in the early diagnosis of cardiovascular diseases, serving as a laboratory tool for assessing the efficiency of ongoing therapy and being a prognostic criterion of possible clinical outcomes and a significant indicator in risk stratification, remain relevant. Two decades have passed since fibroblast growth factor 21 (FGF21), the 21st member of the FGF family, was identified and cloned. FGF21 is a secreted protein that acts as a metabolic regulator and participates in glucose homeostasis, ketogenesis, and regulation of insulin sensitivity. FGF21 expression is controlled by PPAR alpha receptor, which activates peroxisome proliferation. The liver is the main site of FGF21 production. Extrahepatic tissues such as white adipose tissue, brown adipose tissue, and skeletal muscle also express FGF21. Human FGF21 contains 209 amino acids, whereas the mouse counterpart has 210. Mouse and human FGF21 have 75% homology. Endocrine actions of FGF21 include enhancing glucose uptake by adipocytes of white adipose tissue via a unidirectional glucose transporter protein and activating the thermogenic function of brown adipose tissue. Furthermore, FGF21 has autocrine/paracrine effects, such as the induction of hepatic ketogenesis. FGF21 affects target cells with the participation of FGFR1 and FGFR4 receptors and beta-Klotho, a single-pass transmembrane protein that functions as an obligate cofactor of FGF21 signaling. Animal studies have clearly demonstrated that FGF21 acts directly on cardiac tissue, preventing the development of cardiac hypertrophy and reducing post-infarction damage and diabetic cardiomyopathy. Accumulating data emphasize the value of FGF21 as a new biological marker for diagnosis and prognosis assessment in patients with cardiac issues. Moreover, the role of FGF21 in heart diseases is very interesting because of its cardioprotective effects. Future large-scale prospective studies are necessary to confirm of the diagnostic, predictive, and possibly therapeutic role of this marker.

Benzene Exposure Leads to Lipodystrophy and Alters Endocrine Activity In Vivo and In Vitro.

Benzene is a ubiquitous pollutant and mainly accumulates in adipose tissue which has important roles in metabolic diseases. The latest studies reported that benzene exposure was associated with many metabolic disorders, while the effect of benzene exposure on adipose tissue remains unclear. We sought to investigate the effect using in vivo and in vitro experiments. Male adult C57BL/6J mice were exposed to benzene at 0, 1, 10 and 100 mg/kg body weight by intragastric gavage for 4 weeks. Mature adipocytes from 3T3-L1 cells were exposed to hydroquinone (HQ) at 0, 1, 5 and 25 μM for 24 hours. Besides the routine hematotoxicity, animal experiments also displayed significant body fat content decrease from 1 mg/kg. Interestingly, the circulating non-esterified fatty acid (NEFA) level increased from the lowest dose (p trend < 0.05). Subsequent analysis indicated that body fat content decrease may be due to atrophy of white adipose tissue (WAT) upon benzene exposure. The average adipocyte area of WAT decreased significantly even from 1 mg/kg with no significant changes in total number of adipocytes. The percentages of small and large adipocytes in WAT began to significantly increase or decrease from 1 mg/kg (all p < 0.05), respectively. Critical genes involved in lipogenesis and lipolysis were dysregulated, which may account for the disruption of lipid homeostasis. The endocrine function of WAT was also disordered, manifested as significant decrease in adipokine levels, especially the leptin. In vitro cell experiments displayed similar findings in decreased fat content, dysregulated critical lipid metabolism genes, and disturbed endocrine function of adipocytes after HQ treatment. Pearson correlation analysis showed positive correlations between white blood cell (WBC) count with WAT fat content and plasma leptin level (r = 0.330, 0.344, both p < 0.05). This study shed light on the novel aspect that benzene exposure could induce lipodystrophy and disturb endocrine function of WAT, and the altered physiology of WAT might in turn affect benzene-induced hematotoxicity and metabolic disorders. The study provided new insight into understanding benzene-induced toxicity and the relationship between benzene and adipose tissue.

Positive Effects of a Mediterranean Diet Supplemented with Almonds on Female Adipose Tissue Biology in Severe Obesity.

It has been suggested that weight-loss-independent Mediterranean diet benefits on cardiometabolic health and diabetes prevention may be mediated, at least in part, through the modulation of white adipose tissue (WAT) biology. This study aimed to evaluate the short-term effects of a dietary intervention based on the Mediterranean diet supplemented with almonds (MDSA) on the main features of obesity-associated WAT dysfunction. A total of 38 women with obesity were randomly assigned to a 3-month intervention with MDSA versus continuation of their usual dietary pattern. Subcutaneous (SAT) and visceral adipose tissue (VAT) biopsies were obtained before and after the dietary intervention, and at the end of the study period, respectively. MDSA favored the abundance of small adipocytes in WAT. In SAT, the expression of angiogenesis genes increased after MDSA intervention. In VAT, the expression of genes implicated in adipogenesis, angiogenesis, autophagy and fatty acid usage was upregulated. In addition, a higher immunofluorescence staining for PPARG, CD31+ cells and M2-like macrophages and increased ADRB1 and UCP2 protein contents were found compared to controls. Changes in WAT correlated with a significant reduction in circulating inflammatory markers and LDL-cholesterol levels. These results support a protective effect of a Mediterranean diet supplemented with almonds on obesity-related WAT dysfunction.

Inhibition of Adipose Tissue Beiging by HIV Integrase Inhibitors, Dolutegravir and Bictegravir, Is Associated with Adipocyte Hypertrophy, Hypoxia, Elevated Fibrosis, and Insulin Resistance in Simian Adipose Tissue and Human Adipocytes.

For people living with HIV, treatment with integrase-strand-transfer-inhibitors (INSTIs) can promote adipose tissue (AT) gain. We previously demonstrated that INSTIs can induce hypertrophy and fibrosis in AT of macaques and humans. By promoting energy expenditure, the emergence of beige adipocytes in white AT (beiging) could play an important role by limiting excess lipid storage and associated adipocyte dysfunction. We hypothesized that INSTIs could alter AT via beiging inhibition. Fibrosis and gene expression were measured in subcutaneous (SCAT) and visceral AT (VAT) from SIV-infected, dolutegravir-treated (SIVART) macaques. Beiging capacity was assessed in human adipose stromal cells (ASCs) undergoing differentiation and being exposed to dolutegravir, bictegravir, or raltegravir. Expression of beige markers, such as positive-regulatory-domain-containing-16 (PRDM16), were lower in AT of SIVART as compared to control macaques, whereas fibrosis-related genes were higher. Dolutegravir and bictegravir inhibited beige differentiation in ASCs, as shown by lower expression of beige markers and lower cell respiration. INSTIs also induced a hypertrophic insulin-resistant state associated with a pro-fibrotic phenotype. Our results indicate that adipocyte hypertrophy induced by INSTIs is involved via hypoxia (revealed by a greater hypoxia-inducible-factor-1-alpha gene expression) in fat fibrosis, beiging inhibition, and thus (via positive feedback), probably, further hypertrophy and associated insulin resistance.

208-LB: Sensory Nerve Neuropeptide Calcitonin Gene–Related Peptide (CGRP) in Adipose Tissue Changes According to Metabolic Status

White adipose tissue (WAT) is the chief energy storage site in the body and is densely innervated by sensory and sympathetic nerves that enable bi-directional neural communication with the central nervous system. The sympathetic neurotransmitter norepinephrine is the best-studied nerve product in WAT, and is known to stimulate lipolysis, browning (development of brown adipocytes in WAT) , thermogenesis, and other metabolically favorable processes. Conversely, sensory nerves in WAT secrete neuropeptides such as calcitonin gene related peptide (CGRP) , a vasodilatory neuropeptide that also impacts lipolysis, but has been vastly understudied. Circulating CGRP levels are known to be increased in obese humans, but given the beneficial metabolic effects of CGRP this may be a case of CGRP receptor resistance, similar to the observed leptin and insulin resistance with obesity. Therefore, a more comprehensive investigation into CGRP’s roles in adipose tissue and the importance of the sensory nerve supply for WAT function and insulin sensitivity is warranted. Using intravital calcium imaging in WAT of mice, we have observed activation of tissue nerves after application of lipids such as 13-HODE, which is an agonist of sensory nerves and leads to CGRP release. Thirty minutes after 13-HODE administration to WAT there was a significant increase in CGRP levels in WAT (by tissue ELISA) , which were reduced at 120min post-treatment. This suggests local lipid levels in WAT may trigger release of this sensory neuropeptide as an interoceptive response. With obesity, in both diet-induced and genetic ob/ob mice, we see increased WAT CGRP, which fits with reports in humans and may be due to chronically elevated tissue lipids. Exercise also increases tissue CGRP levels, perhaps due to an acute need for lipid fuels in this negative energy balance state. Taken together, CGRP is a novel factor in adipose that may be relevant for changing energy balance status and likely contributes to metabolic health. Disclosure G. Mishra: None. J. Willows: None.

Imaging Adipose Tissue Browning using Mitochondrial Complex-I Tracer [18F]BCPP-EF.

Browning of white adipose tissue (WAT) into beige adipocytes has been proposed as a strategy to tackle the ongoing obesity epidemic. Thermogenic stimuli have been investigated with the aim of converting existing white adipose tissue, primarily used for energy storage, into beige adipocytes capable of dissipating energy; however, evaluation is complicated by the dearth of noninvasive methodologies to quantify de novo beige adipocytes in WAT. Imaging with [18F]FDG is commonly used to measure brown adipose tissue (BAT) and beige adipocytes but the relationship between beige adipocytes, thermogenesis and [18F]FDG uptake is unclear. [18F]BCPP-EF, a tracer for mitochondrial complex-I (MC-I), acts as a marker of oxidative metabolism and may be useful for the detection of newly formed beige adipocytes. Mice received doses of the β3-adrenergic agonist CL-316,243 subchronically for 7 days to induce formation of beige adipocytes in inguinal white fat. PET imaging was performed longitudinally with both [18F]FDG (a marker of glycolysis) and [18F]BCPP-EF (an MC-I marker) to assess the effect of thermogenic stimulation on uptake in browning inguinal WAT and interscapular BAT. Treatment with CL-316,243 led to significant increases in both [18F]FDG and [18F]BCPP-EF in inguinal WAT. The uptake of [18F]BCPP-EF in inguinal WAT was significantly increased above control levels after 3 days of stimulation, whereas [18F]FDG only showed a significant increase after 7 days. The uptake of [18F]BCPP-EF in newly formed beige adipocytes was blocked by pretreatment with an adrenoceptor antagonist suggesting that beige adipocyte formation may be associated with the activation of MC-I. However, in BAT, uptake of [18F]BCPP-EF was unaffected by β3-adrenergic stimulation, potentially due to the high expression of MC-I. [18F]BCPP-EF can detect newly formed beige adipocytes in WAT generated after subchronic treatment with the β3-adrenergic agonist CL-316,243 and displays both higher inguinal WAT uptake and earlier detection than [18F]FDG. The MC-I tracer may be a useful tool in the evaluation of new therapeutic strategies targeting metabolic adipose tissues to tackle obesity and metabolic diseases.

Palmitate induces DNA damage and senescence in human adipocytes in vitro that can be alleviated by oleic acid but not inorganic nitrate.

Hypertrophy in white adipose tissue (WAT) can result in sustained systemic inflammation, hyperlipidaemia, insulin resistance, and onset of senescence in adipocytes. Inflammation and hypertrophy can be induced in vitro using palmitic acid (PA). WAT adipocytes have innately low β-oxidation capacity, while inorganic nitrate can promote a beiging phenotype, with promotion of β-oxidation when cells are exposed to nitrate during differentiation.We hypothesized that treatment of human adipocytes with PA in vitro can induce senescence, which might be attenuated by nitrate treatment through stimulation of β-oxidation to remove accumulated lipids. Differentiated subcutaneous and omental adipocytes were treated with PA and nitrate and senescence markers were analyzed.PA induced DNA damage and increased p16INK4a levels in both human subcutaneous and omental adipocytes in vitro. However, lipid accumulation and lipid droplet size increased after PA treatment only in subcutaneous adipocytes. Thus, hypertrophy and senescence seem not to be causally associated. Contrary to our expectations, subsequent treatment of PA-induced adipocytes with nitrate did not attenuate PA-induced lipid accumulation or senescence. Instead, we found a significantly beneficial effect of oleic acid (OA) on human subcutaneous adipocytes when applied together with PA, which reduced the DNA damage caused by PA treatment.

PEA-OXA ameliorates allodynia, neuropsychiatric and adipose tissue remodeling induced by social isolation

Chronic social isolation generates a persistent state of stress associated with obesity along with some neuro-endocrine disorders and central behavioral sequelae (eg anxiety, depression, aggression, and allodynia). In this study, we evaluated the effect of social isolation on body weight, depressive- and anxious-aggressive-like behavior, as well as on phenotypic changes of adipocytes from visceral adipose tissue of control (group-housed) or socially isolated (single-housed) male mice. The effect of treatment with pentadecyl-2-oxazoline (PEA-OXA), a natural alpha2 antagonist and histamine H3 protean partial agonist, on these alterations was also evaluated. Single or group-housed mice treated with vehicle or PEA-OXA underwent body weight, mechanical allodynia, anxious-, depressive- and aggressive-like behavior measurements. Proliferation rate, apoptosis, senescence, expression of fat lineage genes, lipid droplets and proinflammatory cytokines were measured on white adipose tissue adipocytes from group- or single-housed mice. Single housed mice developed weight gain, mechanical allodynia at the von Frey test, aggressiveness in the resident intruder test, depression- and anxiety-like behavior in the tail suspension and hole drop tests, respectively. Single housed mice receiving PEA-OXA showed a general resolution of both, physical-metabolic and behavioral alterations associated with social isolation. Furthermore, adipocytes from the adipose tissue of socially isolated mice showed an evident inflamed phenotype (i.e. a reduced rate of proliferation, apoptosis, senescence, and ROS hyper-production together with an increased expression of IL-1β, IL-10, IL-17, and TNF-α and a decrease of IL-6). The treatment with PEA-OXA on adipocytes from single housed mice produced a protective/anti-inflammatory phenotype with an increased expression of brown adipose tissue biomarker. This study confirms that persistent stress caused by social isolation predisposes to obesity and neuropsychiatric disorders. PEA-OXA, through its multi-target activity on alpha2 adrenoceptor and histamine H3 receptors, which have recently aroused great interest in the neuropsychiatric field, reduces weight gain, systemic pro-inflammatory state, allodynia, and affective disorders associated with social isolation.

Real ambient particulate matter-induced lipid metabolism disorder: Roles of peroxisome proliferators-activated receptor alpha

A growing body of evidence associated particulate matter (PM) exposure with lipid metabolism disorders, yet, the underlying mechanism remains to be elucidated. Among the major lipid metabolism modulators, peroxisome proliferator-activated receptor (PPAR) alpha plays an important role. In the current study, an individually ventilated cage (IVC) system was used to expose C57/B6 mice to real-ambient PM for six weeks, with or without co-treatment of PPAR alpha agonist WY14,643. The general parameters, liver and adipose tissue pathology, serum lipids, metal deposition and lipid profile of liver were assessed. The results indicated that six weeks of real-ambient PM exposure induced dyslipidemia, including increased serum triglycerides (TG) and decreased high density lipoprotein cholesterol (HDL-C) level, along with steatosis in liver, increased size of adipocytes in white adipose tissue (WAT) and whitening of brown adipose tissue (BAT). ICP-MS results indicated increased Cr and As deposition in liver. Lipidomics analysis revealed that glycerophospholipids and cytochrome P450 pathway were most significantly affected by PM exposure. Several lipid metabolism-related genes, including CYP4A14 in liver and UCP1 in BAT were downregulated following PM exposure. WY14,643 treatment alleviated PM-induced dyslipidemia, liver steatosis and whitening of BAT, while enhancing CD36, SLC27A1, CYP4A14 and UCP1 expression. In conclusion, PPAR alpha pathway participates in PM-induced lipid metabolism disorder, PPAR alpha agonist WY14,643 treatment exerted protective effects on PM-induced dyslipidemia, liver steatosis and whitening of BAT, but not on increased adipocyte size of WAT.

A Comprehensive Morphometric Study of Visceral and Subcutaneous Adipose Tissue Depots in Mice, Hamsters and Rats

Adipose tissue morphology of different fat tissue depots can be described using the number of adipocytes and cell surface of adipocytes. This study deals with characteristics and morphometric analysis of white and brown adipose tissue depots in healthy adult laboratory mice, hamsters and rats of both sexes. The number of unilocular adipocytes in white adipose tissue differs from one adipose tissue depot to another, with the largest number of adipocytes in mice and a similar number in hamsters and rats. The smallest surface area and the largest percentage of small unilocular adipocytes were found in mice. White adipose tissue in hamsters and rats was predominantly made out of a larger percentage of medium-sized adipocytes and a smaller percentage of small and medium-sized adipocytes. Uncoupling protein 1 positive multilocular adipocytes were found in classic brown adipose tissue depots with larger percentages in mice (93.20 %) and hamsters (91.30 %), while rats had a smaller percentage (78.10 %). In white and brown adipose tissue, significant differences between species and both sexes within the same species were found, indicating the influence of sexual dimorphism. The presented morphometric results could serve as a basis for further studies concerning experimental animal models of metabolic disorders and obesity.

6-gingerol ameliorates metabolic disorders by inhibiting hypertrophy and hyperplasia of adipocytes in high-fat-diet induced obese mice

ObjectivesAccumulating studies revealed that 6-gingerol, a compound extracted mainly from ginger, treats obesity by preventing hyperlipidemia in vivo induced by high-fat-diet (HFD). The present study intends to further evaluate the efficacy of 6-gingerol in the treatment of obesity and investigate its potential mechanism. MethodsObese mice were established by HFD induction. Bioinformatic analysis was used to predict the possible pathways enrolled by the application of 6-gingerol. Body weight and the levels of blood glucose and lipids were examined and analyzed for the evaluation of the therapeutic effect of 6-gingerol. The size and amounts as well as the status of adipocytes were determined by histological staining. The expression levels of related proteins in adipose tissue were assessed by immunohistochemical staining, immunofluorescent staining, and Western blot analysis. In addition, the expression levels of related mRNA were assessed by RT-qPCR. ResultsHFD induced obesity was significantly curbed by 6-gingerol treatment. Here inhibition mechanism of 6-gingerol is demonstrated on excessive hypertrophy and hyperplasia of adipocytes in white adipose tissue (WAT), which may be related to the regulation of adipocytokines, such as PPARγ, C/EBPα, FABP4 and adiponectin, and the TLR3/IL-6/JAK1/STAT3 axis. Moreover, 6-gingerol treatment suppressed the expressions of IL-1β and CD68 in the liver and AKT/INSR/IRS-1 in epididymal WAT. ConclusionThe results suggested that 6-gingerol could alleviate metabolic inflammation in the liver and insulin resistance to treat obesity. The mechanism is mainly involved in the inhibition of excessive hypertrophy and hyperplasia of adipocytes.

PEX13 is required for thermogenesis of white adipose tissue in cold-exposed mice

Non-shivering thermogenesis (NST) is a heat generating process controlled by the mitochondria of brown adipose tissue (BAT). In the recent decade, ‘functionally’ acting brown adipocytes in white adipose tissue (WAT) has been identified as well: the so-called process of the ‘browning’ of WAT. While the importance of uncoupling protein 1 (UCP1)-oriented mitochondrial activation has been intensely studied, the role of peroxisomes during the browning of white adipocytes is poorly understood. Here, we assess the change in peroxisomal membrane proteins, or peroxins (PEXs), during cold stimulation and importantly, the role of PEX13 in the cold-induced remodeling of white adipocytes. PEX13, a protein that originally functions as a docking factor and is involved in protein import into peroxisome matrix, was highly increased during cold-induced recruitment of beige adipocytes within the inguinal WAT of C57BL/6 mice. Moreover, beige-induced 3 T3-L1 adipocytes and stromal vascular fraction (SVF) cells by exposure to the peroxisome proliferator-activated receptor gamma (PPARγ) agonist rosiglitazone showed a significant increase in mitochondrial thermogenic factors along with peroxisomal proteins including PEX13, and these were confirmed in SVF cells with the beta 3 adrenergic receptor (β3AR)-selective agonist CL316,243. To verify the relevance of PEX13, we used the RNA silencing method targeting the Pex13 gene and evaluated the subsequent beige development in SVF cells. Interestingly, siPex13 treatment suppressed expression of thermogenic proteins such as UCP1 and PPARγ coactivator 1 alpha (PGC1α). Overall, our data provide evidence supporting the role of peroxisomal proteins, in particular PEX13, during beige remodeling of white adipocytes.

Review on Adiponectin: A Benevolent Adipokine

Adiponectin is a most abundant secretory protein produced by adipocytes of white adipose tissue. Adiponectin circulates in blood as three different (high-molecular, middle-molecular, and low-molecular weight) isoforms, gives its effects through AdipoR1 and AdipoR2 receptor. Primary data suggesting that adiponectin has insulin-sensitizing, anti-atherogenic, and anti-inflammatory effects. High serum level of adiponectin is positively associated with inflammation severity and pathological progression in chronic kidney disease, liver disease and inflammatory bowel disease. It has emerged as a valuable biomarker for insulin sensitivity, cardiovascular risk and inflammation. Adiponectin is gaining attention for its therapeutic role in Alzheimer’s disease. Adiponectin appears to play a crucial role not only in glucose and lipid metabolism but also the development and progression of different cancers. Adiponectin also produced locally in the retinas participate in defense of various eye diseases. This review summarizes the role of adiponectin as benevolent adipokine in different disorders.