Search Results (126)

The most frequently used laboratory animals for studies on adipose tissue properties and obesity are rodents. However, there are significant differences in the types of visceral fat depots between rodents and humans, including fat depots in the heart area. The large human fat depot of greatest interest in cardiac research is the epicardial adipose tissue (EAT). Its properties are widely investigated, because the EAT lies directly on the heart’s surface and can easily affect myocardial physiology. The major fat depot in rodents‘ chest—pericardial fat—is located on the ventral surface of the parietal lamina of the pericardium and is often incorrectly referred to as the EAT. Further confusion arises from reports claiming that rodents are entirely devoid of the EAT. We decided to verify adipose tissues in the heart area of 16 male Sprague Dawley rats under physiological conditions and in obesity. The animals in the NFD group (n = 8) were fed with a standard diet while these in the HFD group (n = 8) were fed with a high-fat diet (31% fat) starting from 4 weeks after birth. When the animals reached 12 weeks, the presence of fat deposits was verified. Additionally, their blood was collected to characterize carbohydrate and lipid metabolism changes, adipokine profile alterations, and their systemic inflammation status. The obesogenic diet caused significant disturbances in their carbohydrate and lipid metabolism, as well as hyperleptinemia. A high-fat diet primarily promoted the accumulation of pericardial fat, which was absent in the NFD rats and observed in 6 out of the 8 HFD animals. In both groups, adipocytes were also found directly on the hearts’ surfaces (EAT), albeit in very small numbers and limited to the atrioventricular groove on the dorsal side of the hearts. These adipocytes were dispersed among the vessels, making quantitative assessment and separation difficult, however, macroscopic evaluation revealed no noticeable differences in its extent. In conclusion, although rats are not entirely devoid of the EAT, their suitability for studying the properties of the EAT appears to be considerably limited. Full article

N-acetylaspartate (NAA) is the second most abundant metabolite in the human brain. Quantifiable amounts of NAA are also present in the blood, but its role in the peripheral tissues is largely unknown. First, we determined the acute effects of insulin administration on NAA concentrations; second, we assessed whether circulating NAA levels associate with markers of central and peripheral insulin sensitivity. A total of 24 persons living with obesity and 19 healthy, lean controls, without neurological disorders, underwent a euglycemic hyperinsulinemic clamp combined with fluorodeoxyglucose positron emission tomography ([¹⁸F]FDG-PET) imaging of the brain, abdomen, and femoral area. Plasma concentrations of NAA were measured at baseline and ~2 h into the clamp using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS-MS). Glucose uptake (GU) rates were analysed using a fractional uptake rate. Serum acetate levels were also assessed using nuclear magnetic resonance (NMR) metabolomics. From baseline to steady-state, insulin levels increased from a mean level of 66 to 447 pmol/L (p < 0.0001). Over this period, circulating NAA concentrations decreased by 5% (p = 0.01), similarly in both groups. The change in NAA was inversely related with the change in plasma acetate (r = −0.36, p = 0.048). Circulating NAA was associated with waist–hip ratio (rho = −0.54, p = 0.0002), steady-state free fatty acids (rho = −0.44, p = 0.003), and directly with HDL cholesterol (rho = 0.54, p = 0.0002), adiponectin (rho = 0.48, p = 0.003), and whole-body insulin sensitivity (rho = 0.34, p = 0.03). Circulating NAA was directly related with skeletal muscle (rho = 0.42, p = 0.01) and visceral adipose tissue GU (rho = 0.41, p = 0.02). Insulin administration leads to a small decrease in circulating NAA levels, and NAA associates consistently with markers of insulin sensitivity. While plasma NAA may be relevant to aspects of whole-body homeostasis, mechanistic insights are needed. Full article

Obesity is a growing global health concern, contributing to diseases such as cancer, autoimmune disorders, and neurodegenerative conditions. Adipose tissue dysfunction, characterized by abnormal adipokine secretion and chronic inflammation, plays a key role in these conditions. Adipose-derived extracellular vesicles (ADEVs) have emerged as critical mediators in obesity-related diseases. However, the study of mature adipocyte-derived EVs (mAdipo-EVs) is limited due to the short lifespan of mature adipocytes in culture, low EV yields, and the low abundance of these EV subpopulations in the circulation. Additionally, most studies rely on rodent models, which have differences in adipose tissue biology compared to humans. To overcome these challenges, we developed a standardized approach for differentiating human preadipocytes (preAdipos) into mature differentiated adipocytes (difAdipos), which produce high-yield, human adipocyte EVs (Adipo-EVs). Using visceral adipose tissue from bariatric surgical patients, we isolated the stromal vascular fraction (SVF) and differentiated preAdipos into difAdipos. Brightfield microscopy revealed that difAdipos exhibited morphological characteristics comparable to mature adipocytes (mAdipos) directly isolated from visceral adipose tissue, confirming their structural similarity. Additionally, qPCR analysis demonstrated decreased preadipocyte markers and increased mature adipocyte markers, further validating successful differentiation. Functionally, difAdipos exhibited lipolytic activity comparable to mAdipos, supporting their functional resemblance to native adipocytes. We then isolated preAdipo-EVs and difAdipo-EVs using tangential flow filtration and characterized them using bulk and single EV analysis. DifAdipo-EVs displayed classical EV and adipocyte-specific markers, with significant differences in biomarker expression compared to preAdipo-EVs. These findings demonstrate that difAdipos serve as a reliable surrogate for mature adipocytes, offering a consistent and scalable source of adipocyte-derived EVs for studying obesity and its associated disorders. Full article

Background/Objectives: Visceral adipose tissue (VAT) may play a direct role in the development of metabolic dysfunction-associated steatotic liver disease (MASLD) and its progression to metabolic dysfunction-associated steatohepatitis (MASH). In this study, we employed untargeted proteomics analyses on paired biopsies from VAT and liver tissues of patients with obesity, MASLD, and MASH. Our objective was to investigate tissue-specific protein expression patterns in search of a potential proteomic signature associated with MASH in both VAT and liver tissue. Methods: VAT and liver tissue were collected from 70 subjects with severe obesity (SWOs) and nine control study subjects without obesity (CON). SWOs were stratified on the basis of liver histology into LS− (no liver steatosis), LS+ (liver steatosis), and MASH. Peptides were extracted from frozen tissue and were analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Raw files were analyzed with Spectronaut, proteins were searched against the human FASTA Uniprot database, and the significantly expressed proteins in the two tissues were analyzed. The p-values were false discovery rate (FDR) corrected. Results: A total of 59 VAT and 42 liver proteins were significantly differentially expressed between the four groups: LS−, LS+, MASH, and CON. The majority were upregulated, and many were related to lipid metabolism. In VAT, only one protein, the mitochondrial sulfide:quinone oxidoreductase (SQOR), was significantly downregulated in the MASH group only. In liver tissue from patients with MASH, six proteins were significantly altered compared with the three other groups. Correlation analyses between the top 10 positive VAT and liver proteins were dominated by inflammatory and detoxification proteins. Conclusions: The presence of MASH was not reflected in the VAT proteome, and both the VAT and the liver proteome were generally affected more by the presence of obesity than by MASLD severity. Several immunomodulating proteins correlated significantly between VAT and liver tissue and could reflect common pathophysiological characteristics. Full article

Background/Objectives: The increasing prevalence of metabolic disorders underscores the need for effective interventions to mitigate environmental stressors such as diesel particulate matter (DPM), a major urban air pollutant. DPM is composed of fine carbonaceous particles that can induce systemic inflammation. This phenomenon results in metabolic dysfunction such as adipocyte hypertrophy, insulin resistance, and mitochondrial impairment in body tissues. Methods: This study investigated the impact of DPM exposure on murine lung, skeletal muscle, and adipose tissues and evaluated the protective effects of supplementation with sodium copper chlorophyllin (SCC). Results: Compared to controls, DPM-exposed mice exhibited significantly elevated oxidative stress markers (* p ≤ 0.05), systemic pro-inflammatory cytokines including TNF-α, MCP-1, IL-6, and IL-1β (* p ≤ 0.05), and adipocyte hypertrophy of both subcutaneous and visceral fat depots, supporting prior findings of DPM-induced metabolic dysfunction. SCC supplementation restored pulmonary ATP levels (* p ≤ 0.05), significantly reduced ROS production in lung and muscle tissue (* p ≤ 0.05), and significantly attenuated DPM-induced inflammatory cytokine secretion (* p ≤ 0.05), while lessening DPM-induced adipocyte hypertrophy. Conclusions: These effects highlight the antioxidant and anti-inflammatory potential of SCC, which likely mitigates systemic metabolic compromise by modulating mitochondrial function and inflammatory pathways. This study further demonstrated that SCC supplementation may be an effective intervention for alleviating the adverse effects of DPM exposure on metabolic and inflammatory compromise. Additional research may clarify a role for SCC in reducing systemic health risks associated with air pollution and offer a foundation for future translational research in human populations exposed to environmental pollutants. Full article

Background: Chronic low-grade inflammation in obesity is linked to white adipose tissue (WAT) dysfunction. Plasma lipopolysaccharide (LPS) activates Toll-like receptor 4 (TLR4), triggering NF-κB and worsening these disturbances. Previously, we showed that histone H3 lysine 27 (H3K27) epigenetic modifications affect WAT gene expression in high-fat-diet mice, identifying key pathways in adipose-derived stem cells (ASCs). This study explores whether NF-κB influences H3K27 modifiers in human ASCs and evaluates fish oil (FO) as a modulator. Methods: Human visceral WAT ASCs were stimulated with LPS and treated with FO enriched with eicosapentaenoic acid (EPA). Flow cytometry, PCR array, RT-PCR, and Western blot assays were used. Results: LPS increased NF-κB activity, elevating KDM6B demethylase levels and H3K27 acetylation. These epigenetic modifications in LPS-stimulated ASCs were associated with persistent changes in the expression of genes involved in adipogenesis, metabolic regulation, and inflammation, even after LPS removal and cell differentiation. FO mitigated these effects, reducing H3K27 acetylation and promoting methylation. Conclusions: FO demonstrates potential in modulating inflammation-induced epigenetic changes and preserving adipocyte function. Full article

Background: Obesity and aging are associated with the progressive loss of brown adipose tissue (BAT), an increase in visceral white adipose tissue (vWAT), and a reduction in subcutaneous white adipose tissue (sWAT). The progressive expansion of visceral obesity promotes a low grade of systemic chronic inflammation (meta-inflammation), contributing to the onset of comorbidities such as type 2 diabetes mellitus (T2DM), metabolic syndrome, and even cancer. Thus, preserving the thermogenic activity of adipose tissue and improving the metabolic flexibility of sWAT could be an effective strategy to prevent the development of metabolic chronic diseases and promote healthy aging. Precision nutrition has emerged as a complementary approach to control the metabolic alterations associated with unhealthy obesity and aging. In a previous work, we described that a silymarin-enriched extract from milk thistle (Mthistle) increased markers of browning and thermogenesis in vitro in human differentiated adipocytes (SGBS). Objectives/Methods: Therefore, this study aims to evaluate the potential of Mthistle to activate thermogenesis in a preclinical model of high-fat diet (HFD)-induced obesity (DIO). Results: Our results demonstrate that Mthistle increases systemic energy expenditure (EE), preserves body temperature after cold exposure, improves insulin resistance, and reduces inflammatory markers in WAT. Conclusions: Based on these results, silymarin-enriched extract from Mthistle may be proposed as a nutraceutical for the management of metabolic chronic diseases and/or accelerated aging. Full article

Background/Objectives: In vitro studies suggest that carnosine reduces inflammation by upregulating anti-inflammatory mediators and downregulating pro-inflammatory cytokines. However, human clinical trials examining the effects of carnosine on inflammatory biomarkers are scant. We conducted a secondary analysis of a double-blind randomised controlled trial (RCT) to examine the effects of carnosine supplementation on inflammatory markers and adipokines in participants with prediabetes or well-controlled type 2 diabetes (T2D). Methods: Out of 88 participants who were recruited, 49 adults with prediabetes or well-controlled T2D (HbA1c: 6.6 ± 0.7% [mean ± SD]) who were treated with diet and/or metformin were eligible for inclusion. Participants were randomised to receive 2 g/day of carnosine or a matching placebo for 14 weeks. We measured serum concentrations of monocyte chemoattractant protein-1 (MCP-1), interleukin (IL)-6, IL-10, C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), adiponectin, leptin, adipsin, serpin, and resistin levels at baseline and after 14 weeks. The trial was registered at clinicaltrials.gov (NCT02917928). Results: Forty-one participants (M = 29/F = 12) aged 53 (42.6, 59.3) years [median (IQR)] completed the trial. After 14 weeks of supplementation, changes in pro- and anti-inflammatory cytokine and adipokine levels did not differ between the carnosine and placebo groups (p > 0.05 for all). The results remained unchanged after adjustment for confounders including age, sex, and anthropometric measures (e.g., body fat percentage and visceral adipose tissue). Conclusions: In individuals with prediabetes and well-controlled T2D, carnosine supplementation did not result in any significant changes in inflammatory markers. Larger RCTs with longer follow-up durations are needed to evaluate whether carnosine may be beneficial in individuals with poorly controlled T2D. Full article

Background: Zinc (Zn), a fundamental trace element in human biology, exhibits pivotal roles in sustaining vital physiological processes and regulating metabolic homeostasis. Insufficient zinc intake has been linked to deleterious consequences on growth, reproductive functions, metabolic activities, and immune responses in both humans and animals. Oral zinc supplementation is usually performed to meet zinc requirement. Previous studies have shown that long-term supplementation of zinc in mice impaired AKT signaling and induced adipocyte hypertrophy in visceral adipose tissue. Methods: The presented study was conducted to investigate the role and mechanism of short-term zinc supplementation on lipids metabolism. Zinc sulfate was supplemented in the drinking water of C57/BL6J male mice at 30 ppm or 90 ppm for one week. Water consumption, food intake, and body weight were analyzed, adipose tissue and serum profile of metabolites were investigated, and the key genes related to lipid metabolism were analyzed. Results: Short-term zinc supplementation decreased visceral adipose tissue weight and adipocyte size compared to the control group, but no difference was observed in food intake, water consumption, and body weight between the two groups. Further studies revealed that short-term zinc supplementation significantly increased the serum insulin level while decreasing the serum NEFA content. In addition, zinc supplementation increased the expression of Atgl and Hsl in the visceral adipose tissue compared with the control mice. Furthermore, the phosphorylation level of HSL and protein level of PPARg in the epididymal adipose tissue increased by zinc supplementation compared with the control mice. In comparison, the protein level of FASN was down-regulated by short-term zinc supplementation in the epididymal adipose tissue, although the expression of lipogenic genes was not changed. The expression of F4/80 and Tnfa were increased in zinc-supplemented adipose tissue as compared with the control group. Conclusions: Our findings suggest that short-term zinc supplementation might reduce fat deposition by enhancing lipolysis in mice. Future studies could focus on the effect of intermittent zinc supplementation on fat reduction in both animal models and humans. Full article

Bone has traditionally been viewed in the context of its structural contribution to the human body. Foremost providing necessary support for mobility, its roles in supporting calcium homeostasis and blood cell production are often afterthoughts. Recent research has further shed light on the ever-multifaceted role of bone and its importance not only for structure, but also as a complex endocrine organ producing hormones responsible for the autoregulation of bone metabolism. Osteocalcin is one of the most important substances produced in bone tissue. Osteocalcin in circulation increases insulin secretion and sensitivity, lowers blood glucose, and decreases visceral adipose tissue. In males, it has also been shown to enhance testosterone production by the testes. Neuropeptide Y is produced by various cell types including osteocytes and osteoblasts, and there is evidence suggesting that peripheral NPY is important for regulation of bone formation. Hormonal disorders are often associated with abnormal levels of bone turnover markers. These include commonly used bone formation markers (bone alkaline phosphatase, osteocalcin, and procollagen I N-propeptide) and commonly used resorption markers (serum C-telopeptides of type I collagen, urinary N-telopeptides of type I collagen, and tartrate-resistant acid phosphatase type 5b). Bone, however, is not exclusively comprised of osseous tissue. Bone marrow adipose tissue, an endocrine organ often compared to visceral adipose tissue, is found between trabecula in the bone cortex. It secretes a diverse range of hormones, lipid species, cytokines, and other factors to exert diverse local and systemic effects. Full article

Obesity is a risk factor for type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Adipose tissue (AT) extracellular vesicles (EVs) could play a role in obesity and T2DM associated CVD progression via the influence of their specific cargo on gene expression in recipient cells. The aim of this work was to evaluate the effects of AT EVs of patients with obesity with/without T2DM on reverse cholesterol transport (RCT)-related gene expression in human monocyte-derived macrophages (MDMs) from healthy donors. AT EVs were obtained after ex vivo cultivation of visceral and subcutaneous AT (VAT and SAT, respectively). ABCA1, ABCG1, PPARG, LXRβ (NR1H2), and LXRα (NR1H3) mRNA levels in MDMs as well as in origine AT were determined by a real-time PCR. T2DM VAT and SAT EVs induced ABCG1 gene expression whereas LXRα and PPARG mRNA levels were simultaneously downregulated. PPARG mRNA levels also decreased in the presence of VAT EVs of obese patients without T2DM. In contrast ABCA1 and LXRβ mRNA levels tended to increase with the addition of obese AT EVs. Thus, AT EVs can influence RCT gene expression in MDMs during obesity, and the effects are dependent on T2DM status. Full article

Aim: C1q/TNF-related protein 6 (CTRP6) is a novel adipokine involved in insulin resistance. Thus, we aim to investigate the expression profile of CTRP6 in the plasma, adipose tissue and placenta of GDM patients and mice. Methods: Chinese Han pregnant women (GDM n = 9, control n = 10) with a scheduled caesarean section delivery were recruited. A number of high-fat diet (HFD) induced-pregnancy C57BL/6 mice were chosen as an animal model of GDM. Circulating levels of CTRP6 and adiponectin were examined by ELISA. CTRP6 expression in adipose tissue and placenta were detected by real-time qPCR and WB. Result: Plasma CTRP6 levels were decreased during the first and second trimesters in mice, as well as the second and third trimesters in patients, while they were increased at delivery in GDM patients and mice. Plasma CTRP6 levels were significantly correlated with WBC, systolic pressure, diastolic pressure and fasting blood glucose. Moreover, CTRP6 mRNA expression in the subcutaneous (sWAT) and omental white adipose tissue (oWAT), as well as in the placenta, was significantly higher in GDM human patients at cesarean delivery. Furthermore, the mRNA expression of Ctrp6 was increased in the sWAT and visceral WAT (vWAT), whilst decreased in the interscapular brown adipose tissue (iBAT), of GDM mice at cesarean delivery. Conclusion: Dynamically expressed CTRP6 may be served as a candidate target for treatment of GDM. Full article

This review examines the impact of obesity on the pathophysiology of heart failure with preserved ejection fraction (HFpEF) and focuses on novel mechanisms for HFpEF prevention using a glucagon-like peptide-1 receptor agonism (GLP-1 RA). Obesity can lead to HFpEF through various mechanisms, including low-grade systemic inflammation, adipocyte dysfunction, accumulation of visceral adipose tissue, and increased pericardial/epicardial adipose tissue (contributing to an increase in myocardial fat content and interstitial fibrosis). Glucagon-like peptide 1 (GLP-1) is an incretin hormone that is released from the enteroendocrine L-cells in the gut. GLP-1 reduces blood glucose levels by stimulating insulin synthesis, suppressing islet α-cell function, and promoting the proliferation and differentiation of β-cells. GLP-1 regulates gastric emptying and appetite, and GLP-1 RA is currently indicated for treating type 2 diabetes (T2D), obesity, and metabolic syndrome (MS). Recent evidence indicates that GLP-1 RA may play a significant role in preventing HFpEF in patients with obesity, MS, or obese T2D. This effect may be due to activating cardioprotective mechanisms (the endogenous counter-regulatory renin angiotensin system and the AMPK/mTOR pathway) and by inhibiting deleterious remodeling mechanisms (the PKA/RhoA/ROCK pathway, aldosterone levels, and microinflammation). However, there is still a need for further research to validate the impact of these mechanisms on humans. Full article

Currently, 30% of the global population is overweight or obese, with projections from the World Obesity Federation suggesting that this figure will surpass 50% by 2035. Adipose tissue dysfunction, a primary characteristic of obesity, is closely associated with an increased risk of metabolic abnormalities, such as hypertension, hyperglycemia, and dyslipidemia, collectively termed metabolic syndrome. In particular, visceral fat accretion is considered as a hallmark of aging and is strongly linked to higher mortality rates in humans. Adipokines, bioactive peptides secreted by adipose tissue, play crucial roles in regulating appetite, satiety, adiposity, and metabolic balance, thereby rendering them key players in alleviating metabolic diseases and potentially extending health span. In this review, we elucidated the role of adipokines in the development of obesity and related metabolic disorders while also exploring the potential of certain adipokines as candidates for longevity interventions. Full article

The development of obesity is associated with substantial modulation of adipose tissue (AT) structure. The plasticity of the AT is reflected by its remarkable ability to expand or reduce in size throughout the adult lifespan, which is linked to the development of its vasculature. This increase in AT vasculature could be mediated by the differentiation of adipose tissue-derived stem cells (ASCs) into endothelial cells (ECs) and form new microvasculature. We have already shown that microRNA (miRNA)-145 regulates the differentiation of ASCs into EC-like (ECL) cells. Here, we investigated whether ASCs-differentiation into ECs is governed by a miRNAs signature that depends on fat depot location and /or the metabolic condition produced by obesity. Human ASCs, which were obtained from white AT by surgical procedures from lean and obese patients, were induced to differentiate into ECL cells. We have identified that miRNA-29b-3p in both subcutaneous (s)ASCs and visceral ASCs and miRNA-424-5p and miRNA-378a-3p in subcutaneous (s)ASCs are involved in differentiation into EC-like cells. These miRNAs modulate their pro-angiogenic effects on ASCs by targeting FGFR1, NRP2, MAPK1, and TGF-β2, and the MAPK signaling pathway. We show for the first time that miRNA-29b-3p upregulation contributes to ASCs’ differentiation into ECL cells by directly targeting TGFB2 in both sASCs and visceral ASCs. Moreover, our results reveal that, independent of sASCs’ origin (obese/lean), the upregulation of miRNA-378a-3p and the downregulation of miRNA-424-5p inhibit MAPK1 and overexpress FGFR1 and NRP2, respectively. In summary, both the adipose depot location and obesity affect the differentiation of resident ASCs through the expression of specific miRNAs. Full article