Adiponectin Expression Research Articles

Effects of duration of high-fat diet on adipocyte hyperplasia in rat epididymis.

High-fat diet (HFD) contributes to obesity and enhances the expression of mature adipocyte markers. However, the effect of HFD on adipocyte hyperplasia remains controversial. This may be due to variations in the duration of HFD. This study aimed to investigate the effects of different durations of HFD on adipocyte hyperplasia and the expression of mature adipocyte-related markers in obese rats. We divided 32 Sprague-Dawley rats into four groups: B (standard diet control), H1 (HFD for four weeks), H2 (HFD for eight weeks), and H3 (HFD for 12 weeks). We evaluated the morphological changes in epididymal fat cells, measured serum inflammatory markers using enzyme-linked immunosorbent assay (ELISA) kits, and quantified adipocyte hyperplasia and maturation markers using western blotting. We observed progressive increases in body weight, epididymal fat weight, serum leptin, TNF-α, IL-6, irisin, PPARγ, adiponectin, and FNDC5 protein expression over 8 weeks of HFD. 12 weeks of HFD intervention resulted in significant decreases in irisin, PPARγ, adiponectin, and FNDC5. Concurrently, the expression of perilipin A and ATGL declined with prolonged HFD. Our results suggest that the duration of HFD significantly affects adipocyte ability to undergo hyperplasia in the epididymis of obese rats. Specifically, 4 weeks of HFD did not change the capacity for adipocyte hyperplasia, while 8 weeks of the diet enhanced this capacity. Interestingly, a longer diet duration (12 weeks) led to a decrease in adipocyte hyperplasia.

P0068 Distribution of α4β7 integrin and MAdCAM-1 expression according to the location of intestinal inflammation in a murine model of spontaneous chronic enterocolitis

Abstract Background The selective blockade of α4β7 integrin is a treatment for inflammatory bowel disease (IBD), with different efficacy according to the location of inflammation along the gastrointestinal tract. A more pronounced effect has been reported in patients with predominant colonic inflammation. It may be attributed to differences in the regional expression of adhesion molecules. This study aimed to investigate the expression of α4β7 integrin and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in colon, ileum, and mesentery, using IL-10 knockout (KO) mice as a model of spontaneous chronic enterocolitis. Methods At 20 weeks, the colon, ileum, and mesentery were extracted from IL-10KO and C57BL/6 wild-type (WT) mice. Protein levels of α4β7 integrin and MAdCAM-1 were determined by Western blot in the different tissues. Additionally, pro-inflammatory cytokines (TNF-α and IFN-γ) and epithelial adhesion molecules (Zonula Occludens-1, ZO-1; E-cadherin and Mucin 2, Muc2) expression in the ileum, as well as adiponectin expression in the mesentery, were analyzed using real-time PCR. Results Analysis demonstrated a significant increase in gene expression of the pro-inflammatory cytokines TNF-α and IFN-γ in the ileum of IL-10 KO mice compared with WT mice (p<0.01). In addition, IL-10KO mice exhibited reduced expression of ZO-1, E-cadherin, and Muc2 in the ileum relative to WT mice (p<0.001). IL-10 deficiency also led to a marked decrease in adiponectin expression in the mesentery (p<0.05). We then analyzed the protein level of MAdCAM-1 and α4β7 integrin according to anatomic region. Remarkably, the protein analysis revealed significantly higher levels of MAdCAM-1 (p<0.01) and α4β7 integrin (p<0.05) in the colon of IL-10 KO mice compared to WT. In the ileum, while MAdCAM-1 levels remained unchanged, α4β7 integrin expression was increased in IL-10KO mice (p<0.01). No significant differences in MAdCAM-1 or α4β7 integrin levels were observed in the mesentery between IL-10KO and WT mice Conclusion IL-10-deficient mice develop inflammation in the ileum, accompanied by a reduction in adiponectin production in the mesentery. In this setting, both α4β7 integrin and MAdCAM-1 showed increased expression in the colon, which was not observed in the ileum or mesentery, despite the inflammation. This differential regional expression pattern of adhesion molecules may explain the variation in the efficacy of anti-integrin therapies. Characterizing these patterns in patients with IBD could help identify those who would benefit most from these treatments.

Circulating levels of adiponectin and AdipoR expression in peripheral blood mononuclear cells are associated with lower respiratory tract Infection.

The role of adiponectin (APN) in regulating inflammation is well recognized in metabolic disease, but the dysregulation of APN in lower respiratory tract infection (LRTI) remains controversial. We aimed to measure APN and its signaling receptors, adiponectin receptor (AdipoR), in peripheral blood mononuclear cells (PBMCs) from LRTI patients to explore their potential roles in the LRTI process. A total of 99 LRTI patients from the Second Xiangya Hospital of Central South University were categorized into acute (n=35) and non-acute (n=64), and non-severe (n=62) and severe (n=37) groups. Serum APN was quantified using ELISA, and mRNA levels of PBMC AdipoRs were determined by RT-qPCR. Both levels of APN in circulation and AdipoR1 mRNA were significantly elevated in the LRTI patients (P=2.61E-04; P=2.49E-08), while no statistical difference was observed for AdipoR2. APN levels were increased in the non-acute group compared to the acute group (P=6.06E-04) and AdipoR1 levels were higher in the severe group (P=0.004). Increased APN and AdipoR1 mRNA levels were positively associated with LRTI even after adjustment for sex, age, BMI and blood lipids (OR=1.10; 95% CI 1.04-1.18; P=9.61E-04; OR=2.69; 95% CI 1.29-5.58; P=0.008). Subgroup analyses based on sex, age, and BMI revealed APN elevation in males, ≥65-year-olds, and overweight individuals, with higher AdipoR2 mRNA in females and those under 65; AdipoR1 was uniformly elevated. Additionally, APN was negatively correlated with lymphocyte count in acute and severe subgroup; AdipoR1 was positively correlated with indicators of inflammation in LRTI group. Our study highlights that serum APN and AdipoR1 mRNA in PBMCs are associated with LRTI. Circulating APN and PBMC AdipoR1 have different significances in LRTI acute onset and severity.

Development and characterization of a chicory extract fermented by Akkermansia muciniphila: An in vitro study on its potential to modulate obesity-related inflammation.

Obesity, the fifth leading cause of death globally and linked to chronic low-grade inflammation and development of numerous severe pathologies, is a major public health problem. Fermented foods, probiotics, and postbiotics emerge as promising avenues for combating obesity and inflammation. The aim of our study was to develop and characterize phyto-postbiotics corresponding to prebiotic compounds fermented by gut bacteria, which could act on obesity and related-inflammation. Chicory extract fermented by Akkermansia muciniphila (C-Akm) was selected as the most antioxidant of 20 fermented extracts. The identification of metabolites derived from C-Akm extract has enabled us to detect mostly amino acids, acids, and some polyphenols (daidzein and genistein). The anti-inflammatory and anti-obesity activities of C-Akm extract were studied by testing the extract (50μg/mL) on the polarization of THP-1 into macrophages, the secretion of pro-inflammatory cytokines in LPS-stimulated PBMCs, and the secretion of leptin and adiponectin in adipospheroids derived from human adipose stem cells. Finally, the extract was examined in 3D co-culture model mimicking inflamed obese adipose tissue. We found that C-Akm extract decreased ROS generation, TNF-α and Il-6 gene expression in polarized macrophages, INFγ and IL-17A secretion in LPS-stimulated PBMCs stimulated with LPS. It also decreased leptin expression while increasing adiponectin and HSL expression levels in both adipocytes and co-cultures. In addition, C-Akm extract stimulated adiponectin secretion in the co-culture model. Finally, our in vitro investigations demonstrated the potential benefits of C-Akm extract in the prevention and treatment of obesity-related inflammation.

Sulfur Amino Acid Restriction Mitigates High-Fat Diet-Induced Molecular Alterations in Cardiac Remodeling Primarily via FGF21-Independent Mechanisms.

Background/Objectives: Dietary sulfur amino acid restriction (SAAR) elicits various health benefits, some mediated by fibroblast growth factor 21 (FGF21). However, research on SAAR's effects on the heart is limited and presents mixed findings. This study aimed to evaluate SAAR-induced molecular alterations associated with cardiac remodeling and their dependence on FGF21. Methods: Male C57BL/6J wild-type and FGF21 knockout mice were randomized into four dietary regimens, including normal fat and high-fat diets (HFDs) with and without SAAR, over five weeks. Results: SAAR significantly reduced body weight and visceral adiposity while increasing serum FGF21 levels. In the heart, SAAR-induced molecular metabolic alterations are indicative of enhanced lipid utilization, glucose uptake, and mitochondrial biogenesis. SAAR also elicited opposing effects on the cardiac gene expression of FGF21 and adiponectin. Regarding cellular stress responses, SAAR mitigated the HFD-induced increase in the cardiac expression of genes involved in oxidative stress, inflammation, and apoptosis, while upregulating antioxidative genes. Structurally, SAAR did not induce alterations indicative of cardiac hypertrophy and it counteracted HFD-induced fibrotic gene expression. Overall, most alterations induced by SAAR were FGF21-independent, except for those related to lipid utilization and glucose uptake. Conclusions: Altogether, SAAR promotes cardiac alterations indicative of physiological rather than pathological remodeling, primarily through FGF21-independent mechanisms.

Supernatants from Newly Isolated Lacticaseibacillus paracasei P4 Ameliorate Adipocyte Metabolism in Differentiated 3T3-L1 Cells.

Background:Lacticaseibacillus paracasei (L. paracasei) strains and their postbiotics show potential for managing metabolic disorders such as diabetes and obesity. Two newly isolated L. paracasei strains, M2.1 and P4, were yielded from Formica rufa anthills in Sinite Kamani National Park, Bulgaria. Their metabolic effects on mature 3T3-L1 adipocytes were investigated. Methods: Mature 3T3-L1 adipocytes were treated for 24 h with 10% (v/v) cell-free supernatants (CFSs) of M2.1 or P4. Two experimental (M2.1, P4) and two control groups (mature, untreated adipocytes and mature adipocytes, treated with 10% (v/v) MRS broth) were analyzed for intracellular lipid accumulation, glucose uptake, and the mRNA expression of lipid metabolism and beta-oxidation-related genes. Fold changes in gene expression were assessed using RT-qPCR. Results: Both M2.1 and P4 CFSs enhanced glucose uptake by over 30% compared to the control. P4 demonstrated a more favorable effect by significantly upregulating adipose triglyceride lipase-patatin-like phospholipase domain containing 2, adiponectin, and peroxisomal beta-oxidation enzymes-acyl-coenzyme A oxidase 1, palmitoyl. Intracellular lipid accumulation increased only with M2.1, while P4 supported improved lipid turnover without promoting excessive lipid storage or lipolysis. Conclusions: P4 CFS exhibits the potential to improve adipocyte metabolism by enhancing glucose uptake, promoting beta-oxidation, and increasing adiponectin expression, offering a promising strategy for managing metabolic dysfunctions.

Tetracarpidium conophorum nuts (African walnuts) up-regulated adiponectin and PPAR-γ expressions with reciprocal suppression of TNF-α gene in obesity.

Tetracarpidium conophorum nuts are nutrient-dense Nigerian snacks associated with weight regulation. This study explores the nuts' impact on adipose tissue gene expression associated with low-grade inflammation. Ethanol whole extract (EWE), ethyl-acetate fraction (EAF) and the resulting residue (RES) were orally administered once daily to MSG-induced obese rats for 6 weeks (n = 6). Afterward, the RNA synthesis of inflammation-associated genes was measured, and GC-MS ligands in the extract and fractions were docked against their protein products in silico. The study found that in obese animals, PPAR-γ and Adiponectin expressions were down-regulated, while TNF-α was up-regulated, indicating an increased low-grade inflammatory process in adipose tissue. After 6-week oral treatments with EWE, EAF and RES, PPAR-γ and Adiponectin expressions increased significantly, while TNF-α expression decreased, suggesting the modulation of obesity-induced inflammation in adipose tissue. The in silico molecular docking analysis identified four lead compounds likely responsible for the observed effect, namely 6-Isopropenyl-4,8a-dimethyl-4a,5,67,8,8a-hexahydro-1H-naphthalen-2-one, 9,12,15-Octadecatrienoic methyl ester (Z,Z,Z), 9,12,15-Octadecatrienoic acid and Hexanedioic acid, bis(2-ethylhexyl). Of these compounds, 6-Isopropenyl-4,8a-dimethyl-4a,5,67,8,8a-hexahydro-1H-naphthalen-2-one demonstrated the strongest affinity to the binding cavities of PPARγ (-7.3 kcal/mol), Leptin (-5.2 kcal/mol), Adiponectin (-7.1 kcal/mol) and TNF-α (-6.3 kcal/mol) and was better than the standard drug, Orlistat (-6.7, -4.4, -6.8 and - 4.5 kcal/mol, respectively). The study reveals that T. conophorum nuts possess bioactive compounds/drug candidates that can exert positive modulation, at the molecular level, the low-grade inflammatory process associated with obesity, which normally facilitates the outset of complications.

Modification of adipogenesis and oxidative stress by quercetin: positive or negative impact on adipose tissue metabolism of obese diabetic Zucker rats?

Reactive oxygen species (ROS) play a key role in the regulation of adipogenesis. The aim of our study was to investigate the effect of quercetin (QCT) supplement on obese adipose tissue metabolism of 30-week-old diabetic Zucker rats (ZDF), not well examined yet. QCT was administered orally at dose of 20mg/kg body weight/day for 6 weeks. Adipocytes from subcutaneous adipose tissue (ScWAT) were isolated and their size was evaluated by light microscopy. Gene expression of adipogenic markers in subcutaneous and visceral adipose tissue was determined by real-time PCR and expression of proteins involved in lipid and glucose metabolism was determined in ScWAT by immunoblotting. Obese ZDF rats suffered from diabetes, hyperinsulinemia and had higher index HOMA-IR (Homeostatic Model Assessment for Insulin Resistance). Treatment with QCT had no significant impact on these metabolic disorders in genetic model of obesity and type 2 diabetes used in our study. Nevertheless, QCT reduced expression of inflammatory cytokine tumour necrosis factor alpha in ScWAT and also visceral adipose tissue and up-regulated expression of anti-inflammatory adiponectin in ScWAT. A shift in redox equilibrium was detected via inhibition of pro-oxidant genes by QCT. Furthermore, QCT reduced adipocyte size in ScWAT, down-regulated expression of fatty acid synthase and adipogenic markers, and moreover stimulated expression of proteolytic enzymes. These changes likely resulted in reduced fat deposition in ScWAT, which was reflected in the elevated circulated levels of free fatty acids in QCT-treated obese ZDF rats compared with obese untreated controls. This increase could, at least in part, explain why we did not observe an improvement in systemic metabolic health by QCT in our model. In conclusion, our study suggests that preventive treatment with QCT might be more effective than its administration in the stage of fully developed diabetes, and further research in this area is needed.

Hyperplasia of fat-containing cells with mature adipocyte marker is associated with pancreatic fat enlargement

Abstract Objectives: The purpose was to elucidate the specific characteristics of fat-containing cells in the pancreas and the mechanism of intra-pancreatic fat deposition (IPFD) in humans. Methods: 15 Japanese patients who had undergone pancreatic resection were enrolled and the normal region of pancreatic samples from each patient was examined. To evaluate the characteristics of fat-containing cells, immunostaining for adiponectin and perilipin 1 was performed and the relationships between the pancreatic fat-cell area or clinical parameters, and the density or the diameter of the fat cells was analyzed. Results: Expression of adiponectin in the cytoplasm and perilipin 1 along the plasma membrane were observed in fat-containing cells in the pancreas. The fat-containing cell area had a significant positive correlation with cell density (r = 0.58, p = 0.023). In addition, fat-containing cell density was significantly positively correlated with homeostasis model assessment insulin resistance (HOMA-IR) (r = 0.61, p = 0.045). Fat-containing cell area was not significantly correlated with cell diameter (r = 0.45, p = 0.095). The diameter of fat-containing cells had significant positive correlations with BMI (r = 0.79, p < 0.001), fasting immunoreactive insulin (r = 0.65, p = 0.029) and HOMA-IR (r = 0.80, p = 0.003). Of all fat-containing cells, 10.4% were intralobular cells, and the diameter of intralobular cells showed a tendency for positive correlation with age (r = 0.52, p = 0.057). Conclusions: The characteristics of fat-containing cells in the pancreas indicate that some of them may be mature adipocytes, and fat volume may be increased by hyperplasia of fat-containing cells associated with insulin resistance. Key terms: pancreatic fat, adipocytes markers, hyperplasia of fat-containing cells, insulin resistance.

Protective effect of adiponectin on oxidative stress-induced ovarian granulosa cell senescence in geese

Geese are susceptible to oxidative stress during breeding, leading to senescence of granulosa cells (GCs) and reduced egg production. Adiponectin (ADPN) is a cytokine secreted by adipose tissue that functions to regulate metabolism and antioxidants. However, its role in the regulation of goose GCs is unclear. To investigate this, senescence in primary goose GCs was induced by D-gal and assessed via RT‒qPCR, senescence-associated β-galactosidase (SA-β-gal) staining, immunofluorescence, flow cytometry, and transcriptomics. The effect of ADPN on GC senescence was investigated by overexpressing and knocking down ADPN expression. The results showed that ADPN could alleviate oxidative stress and cell cycle arrest in GCs, reduce the expression of the senescence-associated secretory phenotype (SASP)-related genes IL-6 and IL-8, regulate the metabolic capacity of GCs, reduce the accumulation of SA-β-gal, maintain telomere length, and alleviate the senescence of GCs induced by D-gal. The RNA-seq results provided further evidence for the regulatory effect of ADPN on GC senescence. ADPN was shown to attenuate oxidative stress-induced GC senescence through the AGE (Advanced glycation end products)-RAGE (Receptor of advanced glycation end products) and NOD-like receptor pathways. These findings may contribute to the development of improved theoretical references for improving egg-laying performance and prolonging the service life of geese.

Ponatinib exacerbate renal injury in systemic lupus erythematosus mouse model through PDGFR-PI3K/AKT pathway

Lupus nephritis (LN) is a common clinical complication of systemic lupus erythematosus (SLE). Proliferative lupus nephritis represents the gravest form of LN, and since effective drugs for its treatment are still lacking, tyrosine kinase inhibitors (TKIs) find extensive clinical utility due to their notable impact on suppressing cell proliferation and may serve as potential drugs for LN treatment. However, previous studies on the effects of TKI on LN have been controversial. Ponatinib, a third-generation TKI, lacks studies on its role in LN. This study aimed to investigate the impact of the ponatinib on LN. MRL/lpr mice were evaluated for renal function, autoimmune markers and histopathological changes after oral administration of ponatinib. RNA-seq analysis was performed to explore the molecular pathways involved in ponatinib-induced kidney injury. Ponatinib uniquely exacerbated renal damage in MRL/lpr mice, evidenced by a decline in renal function and acute pathological changes, without affecting lupus-related autoimmune markers. Differential expressed genes analysis and functional enrichment implicate ponatinib-induced renal damage in MRL/lpr mice associated with adiponectin. Furthermore, we verified ponatinib signaling the PI3K/AKT pathway through PDGFRα, potentially influencing high molecular weight adiponectin (HMW ADIPOQ) expression and exacerbating renal damage. In conclusion, this study demonstrates that ponatinib can up-regulate HMW ADIPOQ expression via the PI3K/AKT pathway by inhibiting PDGFRα phosphorylation, highlighting the potential nephrotoxic effects of ponatinib in lupus-prone mice, and underscoring the importance of monitoring renal function in systemic autoimmune diseases patients receiving ponatinib.

1α,25-Dihydroxyvitamin D Downregulates Adipocyte Impact on Breast Cancer Cell Migration and Adipokine Release.

Excess adiposity is associated with a higher risk of breast cancer metastasis and mortality. Evidence suggests that dietary vitamin D inhibits breast cancer metastasis. However, the mechanistic link between vitamin D's regulation of adipocyte metabolism and metastasis has not been previously investigated. Therefore, the purpose of these experiments was to examine the effect of the active form of vitamin D, 1α,25-dihydroxyvitamin D (1,25(OH)2D), on adipocyte release of bioactive compounds and whether the impact on adipocytes leads to inhibition of breast cancer cell migration, an important step of metastasis. Differentiated 3T3-L1 adipocytes were treated with 1,25(OH)2D for two days, followed by either harvesting the adipocytes or collecting adipocyte-conditioned media without 1,25(OH)2D. A transwell migration assay was conducted with vehicle- or 1,25(OH)2D-conditioned media. In order to explore the mechanism underlying effects on breast cancer metastatic capability, the mRNA expression of leptin, adiponectin, insulin-like growth factor (IGF-1), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) was measured in adipocytes following either vehicle or 1,25(OH)2D treatment. Conditioned media from 1,25(OH)2D-treated adipocytes inhibited the migration of metastatic MDA-MB-231 breast cancer cells compared to conditioned media from vehicle-treated adipocytes. Treatment of adipocytes with 1,25(OH)2D decreased mRNA expression of leptin, adiponectin, IGF-1, IL-6, and MCP-1. Consistent with mRNA expression, concentrations of leptin, adiponectin, IGF-1, and IL-6 in adipocyte-conditioned media were decreased with 1,25(OH)2D treatment, although MCP-1 remained unchanged. In summary, these results suggest that 1,25(OH)2D alters adipocyte secretions to prevent breast cancer metastasis.

Activation of G Protein-Coupled Estrogen Receptor 1 (GPER) Attenuates Obesity-Induced Asthma by Switching M1 Macrophages to M2 Macrophages.

The prevalence of obesity-induced asthma increases in women after menopause. We hypothesized that the increase in obese asthma in middle-aged women results from estrogen loss. In particular, we focused on the acute action of estrogen through the G protein-coupled estrogen receptor 1 (GPER), previously known as GPR30. We investigated whether GPER activation ameliorates obesity-induced asthma with a high-fat diet (HFD) using G-1, the GPER agonist, and G-36, the GPER antagonist. Administration of G-1 (0.5 mg/kg) suppressed HFD-induced airway hypersensitivity (AHR), and increased immune cell infiltration, whereas G-36 co-treatment blocked it. Histological analysis showed that G-1 treatment inhibited HFD-induced inflammation, fibrosis, and mucus hypersecretion in a GPER-dependent manner. G-1 inhibited the HFD-induced rise in the mRNA levels of pro-inflammatory cytokines in the gonadal white adipose tissue and lungs, whereas G-36 co-treatment reversed this effect. G-1 increased anti-inflammatory M2 macrophages and inhibited the HFD-induced rise in pro-inflammatory M1 macrophages in the lungs. In addition, G-1 treatment reversed the HFD-induced increase in leptin expression and decrease in adiponectin expression in the lungs and gonadal white adipose tissue. The results suggest that activation of GPER could be a therapeutic option for obesity-induced asthma.

Abstract P361: Characterization of a Constitutive Adiponectin-Cre Rat Reveals Expression in Adipocyte, Endothelial and Neuronal Lineages

Introduction: The Dahl salt-sensitive (DahlSS) rat is a valuable model for studying hypertension and blood pressure regulation. To create new genetic tools for probing gene function specifically within adipose tissues in this model, we engineered a constitutive Adipoq-Cre rat on a DahlSS genomic background using CRISPR-Cas9 genome editing. Methods: A P2A-Cre cassette was inserted in-frame with the endogenous Adiponectin gene (ENSRNOG00065003537) to enable bicistronic expression from the major transcript (Adipoq-201; ENSRNOT00060022350.1). CRISPR targeting was achieved by microinjecting rat zygotes with a ribonucleoprotein (RNP) complex consisting of Cas9 protein and single guide RNA with a target near the stop codon, and a homology-directed repair plasmid template carrying the Cre recombinase cassette. To evaluate the pattern of Cre expression, Adipoq-Cre DahlSS rats were crossed with a Rosa-CAG-LSL-tdTomato LE reporter line (RRRC#: 009389). The progeny were analyzed for tdTomato reporter expression by cryo-fluorescence tomography (CFT) at postnatal day 10 (P10) and 10 weeks of age, using a Xerra TM EMIT imaging platform (50um sections). A Zeiss LSM 880 system was used to image fresh Vectashield-mounted tissues with a Plan-Apochromat 20x objective and a 561nm laser. Results: Strong CFT signal was detected in all examined adipose depots including subcutaneous, gonadal, and retroperitoneal white adipose tissue, interscapular brown adipose tissue, and perivascular adipose tissue (PVAT). Expression was also detected in the CNS. Confocal imaging of mesenteric PVAT and thoracic aorta PVAT revealed expression in adipocytes, endothelial cells, and peripheral nerves. Conclusion: The newly developed constitutive DahlSS Adipoq-Cre recombinase knockin drives expression in white and brown adipose depots but the presence of expression in non-adipocyte cells suggests either developmental or adult adiponectin expression in endothelial and neuronal lineages, limiting its ability to drive strictly adipose-specific gene expression.

Dietary apigenin ameliorates obesity-related hypertension through TRPV4-dependent vasorelaxation and TRPV4-independent adiponectin secretion

BackgroundObesity-related hypertension is a major cardiovascular risk factor. Apigenin, a natural flavonoid in celery, induces vascular dilation via endothelial transient receptor potential channel vanilla 4 (TRPV4) channels. This study aimed to explore apigenin's potential to alleviate obesity-related hypertension in mice and its underlying mechanisms. MethodsThe C57BL/6 and TRPV4 knockout mice were fed a high-fat diet and subjected to dietary intervention with apigenin. Body weight and tail blood pressure of the mice were measured during the feeding. Vascular reactivity was assessed through a DMT wire myograph systems in vitro. The distribution and expression of adiponectin and pro-inflammatory markers in brown fat were detected. Injecting adeno-associated eight (AAV8) viruses into brown adipose tissue (BAT) to determine whether adiponectin is indispensable for the therapeutic effect of apigenin. Palmitic acid (PA) was used in mouse brown adipocytes to examine the detailed mechanisms regulating adiponectin secretion. ResultsApigenin improved vasodilation and reduced blood pressure in obese mice, effects partly blocked in TRPV4 knockout. It also reduced weight gain independently of TRPV4. Apigenin increased adiponectin secretion from BAT; knockdown of adiponectin weakened its benefits. Apigenin downregulated Cluster of differentiation 38 (CD38), restoring Nicotinamide adenine dinucleotide+ (NAD+) levels and activating the NAD+/Sirtuin 1 (SIRT1) pathway, enhancing adiponectin expression. ConclusionsOur study indicates that dietary apigenin is suitable as a nonpharmaceutical intervention for obesity-related hypertension. In mechanism, in addition to improving vascular relaxation through the activation of endothelial TRPV4 channels, apigenin also directly alleviated adipose inflammation and increased adiponectin levels by inhibiting CD38.

The contribution of adiponectin to diabetic retinopathy progression: Association with the AGEs-RAGE pathway

Diabetic retinopathy (DR) is a chronic complication of diabetes. Given that adiponectin plays a key role in DR progression, this study aims to elucidate the molecular mechanisms of sDR progression related to adiponectin. First, we extracted the microarray dataset GSE60436 from the Gene Expression Omnibus (GEO) database to identify hub genes associated with DR. Pathway enrichment analysis revealed a focus on inflammation, oxidative stress, and metabolic disease pathways. Gene Set Enrichment Analysis (GSEA) identified nine significant pathways related to DR. Immune infiltration analysis indicated increased infiltration of fibroblasts and endothelial cells in DR patients. Second, at the gene level, single-cell RNA sequencing (scRNA-seq) results showed a decrease in ADIPOQ gene expression as the disease progressed in our mouse models. At the protein level, ELISA results from sera of 31 patients and 11 control subjects demonstrated significantly lower adiponectin expression in the proliferative diabetic retinopathy (PDR) group compared to controls. Our findings reveal that adiponectin is involved in the advanced glycation end products (AGEs) and receptor of advanced glycation end products (RAGE) axis, as evidenced by hub gene analysis, scRNA-seq, and ELISA. In conclusion, adiponectin acts as a central molecule in the AGEs-RAGE axis, regulated by ADIPOQ, to influence DR progression.

Metabolic responses to albumin deficiency differ distinctly between partial and full ablation of albumin expression in mice

It had been observed that homozygous albumin knockout mice (Alb−/−) exhibit low plasma free fatty acid (FFA) concentration and improved blood glucose regulation. However, it was not yet known to what extent heterozygous albumin knockout (Alb+/−) mice would display a similar phenotype. Alb−/−, Alb+/−, and wild-type (WT) female mice were studied on a low-fat diet (LFD) or high-fat diet (HFD). On both diets, decreased plasma FFA concentration, and improved glucose tolerance test were observed in Alb−/−, but not in Alb+/−, compared to WT. Plasma adiponectin concentration showed greater elevation in Alb−/− than Alb+/−. Consistent with that, adiponectin gene expression was significantly higher in Alb−/− mice than in Alb+/− and WT mice. A dose-dependent response was observed for hepatic Acadl gene expression showing higher Acadl gene expression in Alb−/− mice than in Alb+/− and WT mice. In conclusion, although female Alb+/− mice exhibited some slight differences from WT mice (e.g., increased plasma adiponectin and hepatic Acadl gene expression), Alb+/− mice did not exhibit improved glucoregulation in comparison to WT mice, indicating that a minor suppression of albumin expression is not sufficient to improve glucoregulation. Furthermore, it is now clear that although the response of female mice to HFD might be unique from how males generally respond, still the complete albumin deficiency in Alb−/− mice and the associated FFA reduction is capable of improving glucoregulation in females on this diet. The present results have implications for the role of albumin and FFA in the regulation of metabolism.

Effects of Exhaustive Exercise on Adiponectin and High-Molecular-Weight Oligomer Levels in Male Amateur Athletes.

Physical activity promotes metabolic health and prevents lifestyle-related diseases. Adiponectin is specifically produced by adipose tissue and comes in three forms, differing in terms of weight: trimers (LMW), hexamers (MMW), and high-molecular-weight (HMW) oligomers. The oligomers are associated with the beneficial effects of adiponectin. In this study, we aimed to investigate the impact of a single bout of exhaustive exercise on adiponectin expression in 25 male amateur athletes, divided into two groups, one comprising young adults (YAs) (n = 15), and the other comprising middle-aged adults (MAs) (n = 10). Body fat was estimated through skinfold thickness. Adiponectin levels were assessed at baseline and at 15 min and 24 h post-exercise, while HMW oligomer levels were evaluated at baseline and at 24 h post-exercise. We observed a significant increase in total adiponectin at both 15 min and 24 h after exercise, with there being a more evident effect among the YA subjects. HMW oligomers also increased significantly after exercise both in the total sample and among the YA subjects, but this was not the case in the MA subjects. The increase in adiponectin levels was significantly associated with Powerpeak. Furthermore, a significant inverse correlation was found between basal adiponectin and VO2peak and Powerpeak. In conclusion, a single bout of exhaustive exercise can rapidly and significantly enhance the basal circulating adiponectin concentration, which seems to be negatively associated with maximal aerobic capacity.

Testosterone with Silymarin Improves Diabetes-obesity Comorbidity Complications by Modulating Inflammatory Responses and CYP7A1/ACC Gene Expressions in Rats.

The co-morbidity of DMOB has become increasingly problematic among the world's population because of a high-calorie diet and sedentary lifestyle. DMOB is associated with lower testosterone (TN) levels, the male sex hormone. The phytochemical compound silymarin (SN) exerts antidiabetic activity by modifying β-cells and anti-obesity activity by inhibiting adipogenesis by methylxanthine. The goal of this study was to find out how well testosterone (TN) with silymarin (SN) protects against oxidative stress and inflammation in the liver of the experimental rats with type 2 diabetes (T2D) and obesity (DMOB). The present study evaluates the efficacy of TN and SN combination (TNSN) on the levels of the potential parameters, such as body mass, serum marker enzymes, fasting glucose levels, HbA1c levels, lipid profile, enzymatic and non-enzymatic antioxidants, proinflammatory cytokines, gene expression pathways, and histopathology in a DMOB comorbidity rat model. Male Sprague-Dawley (SD) rats were fed a high-fat diet (HFD) for 20 weeks with an administration of a single dose of streptozotocin (STZ) i.p. injection (30 mg/kg) on the 9th week of the study. The procedure was to develop the DMOB co-morbidity model in the experimental animals. Co-treatment of TN and SN administration were followed throughout the experiment. Rats were sacrificed after overnight fasting to collect serum and liver tissue samples. Samples were analyzed using a clinical chemistry automated analyzer, spectrophotometry, and quantitative real-time PCR (qPCR) methods and protocols. Analyses of body mass changes, serum marker enzymes, fasting glucose levels, HbA1c levels, lipid profiles, enzymatic and non-enzymatic antioxidants, TNF-α, IL-6, adiponectin, CYP7A1, ACC expression pathways, and histopathology showed significant abnormal levels (P ≤ 0.05) in the pathological group. These were efficiently treated to normal by the administration of TNSN. These results concluded that TNSN exerted protective efficacy against the liver abnormalities in the co-morbidity of the DMOB rat model.

Improved ovarian adiponectin system expression in polycystic ovary syndrome treated with exenatide.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that can cause infertility. This experimental study was conducted to elucidate the role of adiponectin signaling in rats with PCOS treated with exenatide. Twenty-eight adult female Wistar rats were divided into four groups of seven. The normal group did not receive any drug. The PCOS+vehicle (Veh) group received estradiol valerate to induce PCOS, then was divided into PCOS +E50 and PCOS+E100 groups and treated with 50 or 100 mg/kg doses of exenatide, respectively. The mRNA expression of adiponectin and adiponectin receptor 1 (Adipo-R1) was evaluated using a semi-quantitative real-time polymerase chain reaction. The results indicated that the level of adiponectin diminished in the PCOS rats while exenatide increased adiponectin expression at both doses. Adiponectin receptor mRNA levels were higher in the PCOS rats than in the normal rats (p<0.05). In addition, exenatide decreased the levels of Adipo-R1 expression. Taken together, our results showed that exenatide may improve PCOS characteristics in rats through the molecular regulation of adiponectin and its receptor.