Adiponectin mRNA Research Articles

White adipose tissue as a target for cadmium toxicity.

Cadmium (Cd) is a widespread heavy metal known as a toxic environmental pollutant. Cd exposure is threatening due to its bioaccumulation trait in living systems that exceeds 35 years without a beneficial biological role. Acute exposure to high Cd doses was reported to impact adipose tissue (AT) function adversely. The main aim of this study is to investigate the effect of low-dose chronic Cd exposure on the genes involved in adipose tissue (AT) functions. Adult male Sprague-Dawley rats were exposed to a low Cd dose (15 mg/kg B.W./day) for 10 weeks. Then, three AT depots-subcutaneous AT (SUB-AT), abdominal AT (AB-AT), and retroperitoneal AT (REtrop-AT) were excised for Cd accumulation measures and gene expression analysis. Adiponectin and leptin gene expression levels were investigated as markers for adipocytes function and homeostasis. Our results showed that Cd accumulated in all the tested adipose depots, but SUB-AT was found to be the depot to most accumulate Cd. Also, it was exhibited that chronic exposure to low Cd doses altered the gene expression of adipocytokines. The levels of adiponectin and leptin mRNA expression were downregulated in all tested AT-depots after Cd exposure. The significant adverse effect on SUB-AT compared to other depots indicates different responses based on AT depots location toward Cd exposure. Collectively, these results suggest a toxic effect of Cd that influenced adipocyte function.

Adiponectin Intervention to Regulate Betatrophin Expression, Attenuate Insulin Resistance and Enhance Glucose Metabolism in Mice and Its Response to Exercise.

Aims: Adiponectin stimulates mitochondrial biogenesis through peroxisome proliferator-activated receptor-coactivator1α (PGC-1α), a major regulator of mitochondrial biogenesis, and its effect on the genesis of insulin resistance is organ-specific. Expressed predominantly in fat and liver tissues, betatrophin is primarily involved in lipid metabolism, and could be a putative therapeutic target in metabolic syndrome and T2D. We hypothesized that the adiponectin pathway may regulate the production and/or secretion of betatrophin in liver. We aimed to determine whether exercise and adiponectin affect betatrophin to improve insulin resistance in mice. Methods: To investigate this hypothesis, we used wild-type C57BL/6 mice subjected to a high-fat diet, an exercise regimen, and i.p. injection of recombinant mouse adiponectin (Acrp30), and adiponectin knockout (Adipoq−/−) mice (C57BL/6 background) subjected to i.p. injection of Acrp30. Results: In Adipoq–/– mice, betatrophin levels in the plasma and liver were upregulated. In mice, plasma and liver betatrophin levels were significantly upregulated following a high-fat diet. Exercise and i.p. Acrp30 downregulated betatrophin levels and increased adiponectin mRNA and protein expression in the plasma and liver. The trend of change in PGC-1α and betatrophin levels in the liver was consistent. Conclusions/interpretation: Exercise reverses pathogenic changes in adiponectin and betatrophin levels in insulin-resistant mice. Exercise increased adiponectin levels and reduced betatrophin levels. Furthermore, exercise reduced betatrophin levels via adiponectin, which modulated the LKB1/AMPK/PGC-1α signaling axis but was not solely dependent on it for exerting its effects.

Short communication: Photoperiod impacts ovarian extracellular matrix and metabolic gene expression in Siberian hamsters

Ovarian cyclicity is variable in adult Siberian hamsters (Phodopus sungorus), who respond to long breeding season photoperiods with follicle development and ovulation, while short photoperiods typical of the non-breeding season induce gonadal atrophy. Recent RNAseq results identified ovarian matrix components and regulators of metabolism as differentially regulated by photoperiod; however, the impact of photoperiod across a full cycle of ovarian regression and recrudescence had not been explored for additional regulators of ovarian metabolism and extracellular matrix components. We hypothesized that matrix and metabolism-related genes would be expressed differentially across photoperiods that mimic breeding and non-breeding season daylengths. Hamsters were housed in one of four photoperiod groups: long day (16 h of light per day: 8 h of dark; LD, controls), short day regressed (8 L:16D; SD, regressed), and females exposed to SD then transferred to LD to stimulate return of ovarian function for 2 (early recrudescence), or 8 (late recrudescence) weeks. Plasma leptin concentrations along with expression of ovarian versican and liver-receptor homolog-1/Nr582 mRNA decreased in SD compared to LD and late recrudescence, while vimentin mRNA expression peaked in early and late recrudescence. Ovarian expression of fibronectin and extracellular matrix protein-1 was low in LD ovaries and increased in regressed and recrudescing groups. Expression of hyaluronidase-2, nectin-2, liver-X receptors-α and-β, and adiponectin mRNA peaked in late recrudescence, with no changes noted for adiponectin receptor-1 and -2. The results offer a first look at the parallels between expression of these genes and the dynamic remodeling that occurs during ovarian regression and recrudescence.

Adipose and Skeletal Muscle Expression of Adiponectin and Liver Receptor Homolog-1 With Weight Loss and Aerobic Exercise.

Adiponectin is an adipokine mainly secreted by adipocytes that regulates the metabolism of lipids and glucose. Liver receptor homolog-1 (LRH-1), also named NR5A2, is a nuclear receptor that regulates lipid metabolism and homeostasis. The purpose of this study was to compare adiponectin and LRH-1 messenger RNA (mRNA) expression in adipose tissue and LRH-1 expression in skeletal muscle between men and women at baseline and to study the effects of aerobic exercise (AEX) training or weight loss (WL) on their expression. This hospital and university setting study included 62 overweight and obese men (n = 23) and women (n = 39) older than 45 years, of whom 41 completed 6 months of WL (n = 21) or AEX (n = 20). Outcomes included abdominal and gluteal adipose tissue and skeletal muscle gene expression. Adiponectin and LRH-1 mRNA expression in adipose tissue and LRH-1 mRNA expression in skeletal muscle is higher in women than in men (P < .05). Adiponectin mRNA expression in gluteal and abdominal adipose tissue did not change significantly after AEX or WL. LRH-1 mRNA expression increased both in adipose tissue and skeletal muscle after AEX (P < .05) and the change in muscle LRH-1 was different between the groups (P < .05). Adiponectin was positively correlated to LRH-1 in adipose tissue (P < .001). The change in maximal oxygen consumption related to the change in LRH-1 mRNA (r = 0.43; P = .01). LRH-1, as a nuclear reporter, may activate adiponectin mRNA expression in adipose tissue and increases after AEX.

Physical activity enhances fecal lactobacilli in rats chronically drinking sweetened cola beverage.

Overweight and obesity have been linked with increased intake of sugar-sweetened beverages. On the other hand, physical activity has been known to lead to weight loss. Therefore, we hypothesized that exercise might influence the Lactobacillus population in fecal microbiota as their changed abundance is often associated with shifts in the physical activity and diet. In our experiment, Wistar rats were allocated into groups with normal feed or added sugar-sweetened beverages with or without access to a running wheel. Interestingly, only a combination of physical activity and sweetened beverage intake was associated with a significant increase in fecal lactobacilli abundance, suggesting a connection between exercise and a rise in lactobacilli abundance. Moreover, physical activity has improved weight-related parameters and led to increased plasma and mRNA adiponectin levels. Ghrelin and leptin plasma levels were unaltered. Taken together, our results demonstrate that effect of physical activity on adiposity even during unhealthy feeding patterns is accompanied by increased lactobacilli abundance in the fecal microbiota population.

Severe Hyperprolactinemia Promotes Brown Adipose Tissue Whitening and Aggravates High Fat Diet Induced Metabolic Imbalance.

BackgroundThe association of high serum prolactin and increased body weight is positive but controversial, therefore we hypothesized that additional factors such as diets and the impact of prolactin on brown adipose tissue may condition its metabolic effects.MethodsWe used LacDrd2KO females with lifelong severe hyperprolactinemia due dopamine-D2 receptor deletion from lactotropes, and slow onset of metabolic disturbances, and compared them to their respective controls (Drd2 loxP/loxP ). Food intake, and binge eating was evaluated. We then challenged mice with a High Fat (HFD) or a Control Diet (CD) for 8 weeks, beginning at 3 months of age, when no differences in body weight are found between genotypes. At the end of the protocol brown and white adipose tissues were weighed, and thermogenic and lipogenic markers studied, using real time PCR (Ucp1, Cidea, Pgc1a, Lpl, adiponectin, Prlr) or immunohistochemistry (UCP1). Histochemical analysis of brown adipose tissue, and glucose tolerance tests were performed.ResultsHyperprolactinemic mice had increased food intake and binge eating behavior. Metabolic effects induced by a HFD were exacerbated in lacDrd2KO mice. Hyperprolactinemia aggravated HFD-induced body weight gain and glucose intolerance. In brown adipose tissue pronounced cellular whitening as well as decreased expression of the thermogenic markers Ucp1 and Pgc1a were observed in response to high prolactin levels, regardless of the diet, and furthermore, hyperprolactinemia potentiated the decrease in Cidea mRNA expression induced by HFD. In subcutaneous white adipose tissue hyperprolactinemia synergistically increased tissue weight, while decreasing Prlr, Adiponectin and Lpl mRNA levels regardless of the diet.ConclusionsPathological hyperprolactinemia has a strong impact in brown adipose tissue, lowering thermogenic markers and evoking tissue whitening. Furthermore, it modifies lipogenic markers in subcutaneous white adipose, and aggravates HFD-induced glucose intolerance and Cidea decrease. Therefore, severe high prolactin levels may target BAT function, and furthermore represent an adjuvant player in the development of obesity induced by high fat diets.

Traditional Sunchang Gochujang Attenuates Obesity in High-Fat Diet Induced Obese Mice

ObjectivesObesity is a major global health crisis. High fat diet (HFD) and salt intake have been linked to leptin resistance and obesity. Korea has lower obesity prevalence relative to other countries, although Koreans consume various fermented substances containing high salt, such as gochujang and doenjang amongst others. This phenomenon is defined as “the Korean paradox”. Gochujang is a Korean fermented pepper paste that contains high amount of salt. Therefore, we aimed to evaluate the anti-obesity potential of traditional gochujang on HFD-induced obese mice by comparing its effects with HFD and HFD containing same amount of salt from traditional gochujang.Methods4 weeks old C57BL/6J male mice were divided into 4 groups and fed a normal diet (ND), HFD (HD), HFD + salt (SALT) and HFD + traditional sunchang gochujang (TS) diets for 14 weeks. Biochemical analyses of serum, liver, and brown and epididymal fat tissues were performed to assess metabolic changes and obesity-related markers. The expressions of mRNA and protein involved in obesity, lipogenesis, adipogenesis and energy expenditure were evaluated from liver, brown and epididymal fat tissues by qPCR and western blot.ResultsTS supplementation significantly reduced obesity in HFD-induced obese mice. Compared to HD, TS had a lower body weight (24%), reduced serum leptin and insulin levels and improved serum and liver lipid profiles. Compared to HD and SALT groups, TS group had a significant reduction of mRNA and protein expressions associated with anabolic lipid metabolism including leptin, PPARγ, CEBPα, FAS, and ACC, while showing significant increase of adiponectin and energy expenditure-related mRNA, such as PPARα and CPT1.ConclusionsTS ameliorates obesity in HFD-induced obese mice by boosting leptin levels and inhibiting the adipogenesis and lipogenesis. Also, SALT group did not show any improvements compared with TS group. These observations imply that high salt content of TS is not a problematic feature. Our findings prove “the Korean paradox” of gochujang and anti-obesity effects of traditional gochujang, proposing the possibility of the traditional gochujang as a functional food against obesity.Funding SourcesMinistry of Agriculture, Food and Rural Affairs and partly Korea Agro-Fisheries and Food trade corporation.

4-Hydroxybenzoic Acid and β-Sitosterol from Cucurbita ficifolia Act as Insulin Secretagogues, Peroxisome Proliferator-Activated Receptor-Gamma Agonists, and Liver Glycogen Storage Promoters: In Vivo, In Vitro, and In Silico Studies.

Insulin secretion and GLUT4 expression are two critical events in glucose regulation. The receptors G-protein-coupled receptor 40 (GPR40) and peroxisome proliferator-activated receptor-gamma (PPARγ) modulate these processes, and they represent potential therapeutic targets for new antidiabetic agent's design. Cucurbita ficifolia fruit is used in traditional medicine for diabetes control. Previous studies demonstrated several effects: a hypoglycemic effect mediated by an insulin secretagogue action, antihyperglycemic effect, and promoting liver glycogen storage. Anti-inflammatory and antioxidant effects were also reported. Moreover, some of its phytochemicals have been described, including d-chiro-inositol. However, to understand these effects integrally, other active principles should be investigated. The aim was to perform a chemical fractionation guided by bioassay to isolate and identify other compounds from C. ficifolia fruit that explain its hypoglycemic action as insulin secretagogue, its antihyperglycemic effect by PPARγ activation, and on liver glycogen storage. Three different preparations of C. ficifolia were tested in vivo. Ethyl acetate fraction derived from aqueous extract showed antihyperglycemic effect in an oral glucose tolerance test and was further fractioned. The insulin secretagogue action was tested in RINm5F cells. For the PPARγ activation, C2C12 myocytes were treated with the fractions, and GLUT4 mRNA expression was measured. Chemical fractionation resulted in the isolation and identification of β-sitosterol and 4-hydroxybenzoic acid (4-HBA), which increased insulin secretion, GLUT4, PPARγ, and adiponectin mRNA expression, in addition to an increase in glycogen storage. 4-HBA exhibited an antihyperglycemic effect, while β-sitosterol showed hypoglycemic effect, confirming the wide antidiabetic related results we found in our in vitro models. An in silico study revealed that 4-HBA and β-sitosterol have potential as dual agonists on PPARγ and GPR40 receptors. Both compounds should be considered in the development of new antidiabetic drug development.

Digested protein from chia seed (Salvia hispanica L) prevents obesity and associated inflammation of adipose tissue in mice fed a high-fat diet

Background and aimOverweight and obesity are associated with the development of several health complications, such as diabetes, cancer, and cardiovascular disease. Chia seed is a rich source of proteins and peptides with potential anti-inflammatory and antioxidant effects. This study aimed to evaluate the effects of digested proteins (DP) from chia seed to prevent adipogenesis and adipose tissue inflammation in mice fed a high-fat diet. Methods and resultsC57Bl/6 black mice were fed a high-fat diet plus DP (400 mg/kg of body/day) for 9 weeks. DP from chia seed reduced levels of plasma total cholesterol (−17.5%), LDL (−42.8%), triacylglycerides (−12.3%), % body fat (−26.98%), and waist circumference (−5.5%) in obese mice (p < 0.05). Furthermore, treatment with DP reduced (p < 0.05) adipocytes area, foci of inflammation, levels of p-NF-κB p65, PPARγ, mRNA SREBP1 (sterol regulatory element-binding transcription), and TNF-α. DP also increased mRNA adiponectin on adipose tissue in animals DP-treated, compared with no-DP-treated animals. However, mRNA LPL and HDL levels were not changed (p > 0.05). The peptides from DP had in silico high interaction with metalloproteinase-2. ConclusionsWhen using this experimental model, DP from chia seed had an anti-inflammatory and anti-adipogenic effect. These results suggest the effectiveness of digested proteins from chia seed against central obesity and its associated inflammation.

Telmisartan is the most effective ARB to increase adiponectin via PPARα in adipocytes.

Telmisartan and irbesartan are angiotensin II receptor blockers (ARBs) and reportedly stimulate adiponectin secretion from adipocytes via partial peroxisome proliferator-activated receptor γ (PPARγ) activation. However, quantitative evaluation among different ARBs has not been performed. Adiponectin exerts strong protection against a number of pathological events by suppressing cell death, inhibiting inflammation, and enhancing cell survival, while leptin promotes inflammation, oxidative stress, atherogenesis, and thrombosis. The aim of this study was to identify the most effective ARB enhancing adiponectin secretion without raising leptin secretion from human white adipocytes (HWAs). Among seven ARBs (azilsartan, candesartan, irbesartan, losartan, olmesartan, telmisartan, and valsartan), telmisartan was the most effective ARB for the increase of adiponectin secretion and irbesartan was the second, whereas the other ARBs at 1 µM had no effect on adiponectin secretion. GW9662, a PPARγ antagonist, completely blocked pioglitazone (PPARγ agonist)-induced adiponectin secretion and mRNA expression, whereas it unexpectedly blocked neither telmisartan- nor irbesartan-induced adiponectin secretion and mRNA expression but rather increased them. GW6471, PPARα antagonist, and siRNA for PPARα suppressed telmisartan- and irbesartan-induced adiponectin secretion, suggesting that PPARα is the main target of these ARBs to increase adiponectin secretion in HWAs. Leptin secretion was not affected by any ARBs at 1 µM and GW9662 significantly decreased the basal secretion of leptin, suggesting that basal leptin secretion is regulated in a PPARγ-dependent manner. We conclude that telmisartan is the most effective ARB to increase adiponectin secretion via PPARα without raising leptin secretion from HWAs.

The Bioactive Flavonoid Taxifolin Inhibits Differentiation and the Production of the Inflammatory Cytokine Interleukin-6 in Cultured Human Adipocytes

Background: Taxifolin, a bioactive flavonoid that possesses potent antioxidant activity, has been reported to show multiple pharmacological properties, including protective effects against obesity-related diabetic nephropathy and diabetic cardiomyopathy. However, knowledge regarding the effects of taxifolin on adipocytes, which are closely associated with obesity and diabetes, is insufficient. Objective: This study aimed to explore the direct effects of taxifolin on differentiation and inflammation adipocytes by culturing human preadepocytes (HPAds). Methods: HPAds were cultured for 16 days in a differentiation medium with or without taxifolin to examine its effect on differentiation. On day 16, levels of lipid and differentiation-related gene expression (PPARγ, C/EBPα, adiponectin, CD36, and GLUT4 mRNAs) in adipocytes were measured using the Oil Red O assay and the real-time polymerase chain reaction assay, respectively. Adiponectin levels in the medium were measured using an enzyme-linked immunosorbent assay (ELISA). The taxifolin effect on inflammation was assessed using mature adipocytes differentiated for 15 days. After incubating mature adipocytes in a differentiation medium containing tumor necrosis factor-α (TNF-α) or TNF-α + taxifolin for three hours, the level of interleukin-6 (IL-6), an inflammatory cytokine in the medium, was measured using ELISA. Results: Exposure of taxifolin to adipocytes during differentiation decreased the levels of lipid in adipocytes and adiponectin in the medium. It also decreased the expression levels of C/EBPα, adiponectin, CD36, and GLUT4 mRNAs, but not PPARγ mRNA. Taxifolin inhibited the increase in IL-6 levels in the medium induced by TNF-α in mature adipocytes. Conclusion: These results suggest that taxifolin has anti-differentiation and anti-inflammatory effects on adipocytes. Additionally, taxifolin is expected to have the potential as a therapeutic drug for obesity and metabolic syndrome.

Adding collagen to adipose tissue transplant increases engraftment by promoting cell proliferation, neovascularisation and macrophage activity in a rat model.

To clarify the effect of collagen addition to transplanted adipose tissue on angiogenesis, cell proliferation and tissue remodelling process and reveal whether collagen addition contributes to improving transplanted adipose tissue engraftment in rats. Adipose tissue was harvested from the inguinal and injected into the back of the rat, in addition to collagen. Engraftment tissue was harvested, semi‐quantitatively evaluated and underwent haematoxylin and eosin or Perilipin staining. Moreover, we evaluated viable adipocyte counts and neovascularisation. Macrophages were evaluated using flow cytometry, and the adiponectin or vascular endothelial growth factor (VEGF) mRNA was detected using real‐time polymerase chain reaction. By collagen addition to transplanted adipose tissue, higher engraftment rate semi‐quantitatively and a greater number of new blood vessels histologically were identified. Perilipin staining revealed a higher adipocyte number. The total cell, M1 macrophage and M2 macrophage count were higher. There was increased adiponectin mRNA significantly at week 4 compared to that at week 1 after transplantation. Note that the expression levels of VEGF mRNA increased. In rats, adding collagen enhanced cell proliferation, induced M2 macrophages, which are involved in wound healing, and promoted adipocytes and neovascularisation. Therefore, collagen addition to transplanted adipose tissue could increase the engraftment rate of adipose tissue.

Glucocorticoid/Adiponectin Axis Mediates Full Activation of Cold-Induced Beige Fat Thermogenesis.

Glucocorticoids (GCs), a class of corticosteroids produced by the adrenal cortex in response to stress, exert obesity-promoting effects. Although adaptive thermogenesis has been considered an effective approach to counteract obesity, whether GCs play a role in regulating cold stress-induced thermogenesis remains incompletely understood. Here, we show that the circulating levels of stress hormone corticosterone (GC in rodents) were significantly elevated, whereas the levels of adiponectin, an adipokine that was linked to cold-induced adaptive thermogenesis, were decreased 48 h post cold exposure. The administration of a glucocorticoid hydrocortisone downregulated adiponectin protein and mRNA levels in both WAT and white adipocytes, and upregulated thermogenic gene expression in inguinal fat. In contrast, mifepristone, a glucocorticoid receptor antagonist, enhanced adiponectin expression and suppressed energy expenditure in vivo. Mechanistically, hydrocortisone suppressed adiponectin expression by antagonizing PPARγ in differentiated 3T3-L1 adipocytes. Ultimately, adiponectin deficiency restored mifepristone-decreased oxygen consumption and suppressed the expression of thermogenic genes in inguinal fat. Taken together, our study reveals that the GCs/adiponectin axis is a key regulator of beige fat thermogenesis in response to acute cold stress.

Abstract P158: Endothelin Inhibits Adiponectin Production Via ETB Receptor Activation On Adipocytes

Endothelin-1 has been implicated in obesity related insulin resistance. Our lab recently demonstrated that ET-1 is elevated in adipose tissue of obese mice, and blockade of ET-1 receptors improves insulin sensitivity in a mouse model of diet induced obesity. One potential mechanism by which ET-1 promotes insulin resistance is through activation of the ET-1 type B receptor (ET B ). Blockade of ET B receptors improves insulin sensitivity and increases circulating adiponectin, an adipokine only released by adipose tissue. Therefore, the current hypothesis is that ET-1 causes insulin resistance and inhibits adiponectin production by adipocytes. Primary mouse adipocytes were cultured and chronically treated with ET-1 for 3 days. ET-1 treated adipocytes had significantly lower peroxisome proliferator activator gamma, a transcription factor that drive adiponectin production, and adiponectin mRNA expression and release into media. This response was attenuated by co-treatment with an ET B receptor antagonist (BQ-788; 57.2±2.0 vehicle, 42.5±4.5 ET-1, 59.8±1.5 ET-1+BQ788, ng/ml; p&lt;0.05) and in adipocytes from adipocyte ET B receptor knockout mice. Further, expression of several genes in the insulin signaling pathway, including Glut4 and insulin receptor substrates 1 and 2 were significantly reduced in adipocytes treated with ET-1, a response that was attenuated with ET B receptor blockade or knockout of the ET B receptor. These data suggest that increased ET-1 production in adipose tissue promotes insulin resistance on adipocytes and inhibits the release of insulin sensitizing adipokines such as adiponectin, a potential mechanism by which ET-1 receptor blockade improves insulin sensitivity in obese mice.

Targeting Adenosine Receptor by Polydeoxyribonucleotide: An Effective Therapeutic Strategy to Induce White-to-Brown Adipose Differentiation and to Curb Obesity.

Obesity is a worldwide chronic metabolic disease characterized by an abnormal fat accumulation and represents one of the main risk factors for several diseases. White adipose tissue is the primary site for energy storage in the form of triglycerides, whereas brown adipose tissue does not store energy-providing lipids but rather dissipates it by producing heat. White-to-brown adipocyte trans-differentiation could represent a new target of anti-obesity strategies and result in fat reduction. Previous studies indicated that adenosine receptor activation induces trans-differentiation of white adipocytes to brown adipocytes. The aim of this study was to evaluate the effects of polydeoxyribonucleotide (PDRN), an A2Ar receptor agonist, in an in vitro model of browning. Mouse 3T3-L1 pre-adipocytes were differentiated in mature adipocytes with specific culture media and then treated with PDRN (10 µg/mL), PDRN + ZM241385 (1 µM), CGS21680 (1 µM) and CGS + ZM241385 for 24 h. Cell viability was studied by MTT assay, and browning induction was evaluated by Oil Red O staining and by RT-qPCR to study gene expression of browning markers. PDRN, as well as CGS21680, reduced the accumulation of lipids, cell volume and lipid droplet size; increased the expression of UCP1, PRDM16 and DIO2, considered as browning markers; and reduced the expression of FASn and FABP4, considered as whitening markers. In addition, PDRN decreased leptin expression and enhanced adiponectin mRNA levels. All these effects were abrogated when PDRN was co-incubated with the A2Ar antagonist ZM241385. In conclusion, these results suggest that PDRN is able to induce the white-to-brown adipose differentiation through A2Ar stimulation. Since PDRN is a safe drug already available in the market for other therapeutic indications, its “anti-obesity” potential warrants investigation in a clinical scenario.

The lncRNA H19/miR-541-3p/Wnt/β-catenin axis plays a vital role in melatonin-mediated osteogenic differentiation of bone marrow mesenchymal stem cells.

Implant dentures become the first choice for denture restoration in patients with tooth loss. However, oral implants often fail in osteoporosis (OP) patients. Melatonin (MT) induces osteogenic differentiation of bone mesenchymal stem cells (BMSCs), suggesting its therapeutic potential in OP treatment. Long non-coding RNA H19 induces osteogenic differentiation of BMSCs, while its regulatory mechanism in MT-involved osteogenic and adipogenic differentiation of BMSCs remains elusive. Ovariectomized (OVX) rat was used to construct an OP model, and bone quality was assessed. Meanwhile, the expression of H19, miR-541-3p, MT and adiponectin (APN) was examined by quantitative reverse transcription-PCR (qRT-PCR) or ELISA. The adipogenic and osteogenic differentiation of BMSCs were determined by oil red O staining and alizarin red S staining, respectively. The targeting relationships between H19, miR-541-3p and APN mRNA were predicted by bioinformatics and confirmed by RNA immunoprecipitation and dual-luciferase reporter assay. The results showed that MT, H19 and APN were down-regulated, while miR-541-3p was up-regulated in the OVX rat model. At the cellular level, MT reduced adipogenic differentiation, heightened osteogenic differentiation of BMSCs, and activated Wnt/β-catenin pathway, which were reversed by the MT2 selective inhibitor 4-P-PDOT. Overexpressing H19 facilitated the osteogenic differentiation and inhibited the adipogenic differentiation of BMSCs mediated by MT, while H19 knockdown or overexpressing miR-541-3p had the opposite effect. Moreover, H19 functioned as a competitive endogenous RNA and sponged miR-541-3p, and miR-541-3p targeted APN. Overall, MT modulates the osteogenic and adipogenic differentiation of BMSCs by mediating H19/miR-541-3p/APN axis, providing a new reference for the targeted therapy of OP.

The anti-diabetic effects of NAG-1/GDF15 on HFD/STZ-induced mice

Nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1) plays a role in various diseases. Here, the anti-diabetic effects of NAG-1 were evaluated using a high-fat diet/streptozotocin-induced diabetic mouse model. NAG-1-overexpressing transgenic (NAG-1 Tg) mice exhibited lower body weight, fasting blood glucose levels, and serum insulin levels than wild-type (WT) mice. The homeostatic model assessment of insulin resistance scores of NAG-1 Tg mice were lower than those of WT mice. Hematoxylin and eosin staining revealed a smaller lipid droplet size in the adipose tissues, lower lipid accumulation in the hepatocytes, and larger beta cell area in the pancreas of NAG-1 Tg mice than in those of WT mice. Immunohistochemical analysis revealed downregulated expression of cleaved caspase-3, an apoptosis marker, in the beta cells of NAG-1 Tg mice. Adiponectin and leptin mRNA levels were upregulated and downregulated in NAG-1 Tg mice, respectively. Additionally, the expression of IRS1/PI3K/AKT signaling pathway components, especially Foxo1, which regulates gluconeogenesis in the muscle and white adipose tissue, was downregulated in NAG-1 Tg mice. Furthermore, NAG-1 overexpression promoted the expression of As160 in both muscles and adipocytes, and the mRNA levels of the NLRP3 pathway members were downregulated in NAG-1 Tg mice. Our findings suggest that NAG-1 expression alleviates diabetes in mice.

Hyperbaric oxygen therapy affects insulin sensitivity/resistance by increasing adiponectin, resistin, and plasminogen activator inhibitor-I in rats

Background/aim Hyperbaric oxygen therapy (HBOT) causes insulin sensitivity, but the reason for this is not known yet. The aim of the present study was to investigate the effect of HBOT on insulin sensitivity via resistin, plasminogen activator inhibitor-I (PAI - I), and adiponectin.Materials and methods The study was designed using HBOT and control groups, with eight rats in each group. After 20 days of HBOT under 2.5 atmospheres for 90 min, the fasting insulin (FI), resistin, PAI-I, homeostatic model assessment of insulin resistance scores (HOMA–IR), quantitative insulin sensitivity check index (QUICKI), fasting plasma glucose (FPG), triglyceride, and high-density lipoprotein cholesterol (HDL-C) in the plasma were measured. The resistin, PAI-I, and adiponectin mRNA expression levels were also measured in the adipose tissue.ResultsCompared to the control group, the FI, FPG, and HOMA-IR scores were significantly lower in the HBOT group, whereas the HDL-C and QUICKI scores were found to be higher. In addition, the resistin, adiponectin, and PAI-I mRNA expression levels were also higher in the HBOT group.ConclusionThe present study demonstrated that the HBOT had regulated the FI, FPG, and HDL-C associated with metabolic syndrome and diabetes mellitus. Moreover, the study showed that HBOT causes insulin sensitivity by raising adiponectin.

12\u03b1-Hydroxylated bile acid enhances accumulation of adiponectin and immunoglobulin A in the rat ileum

We previously reported that dietary supplementation with cholic acid (CA), the primary 12α-hydroxylated (12αOH) bile acid (BA), reduces plasma adiponectin concentration in rats. The aim of this study was to examine the distribution of adiponectin in the body of CA-fed rats and its influence on mucosal immunoglobulin A concentration in the intestine. Rats were fed a diet supplemented with or without CA (0.5 g CA/kg diet) for 13 weeks. A reduction in plasma adiponectin level was observed from week 3. At the end of the experiment, the CA diet reduced plasma adiponectin concentration both in the portal and aortic plasma. Accumulation of adiponectin was accompanied by an increase in cadherin-13 mRNA expression in the ileal mucosa of CA-fed rats. No increase was observed in adiponectin mRNA expression in the ileal and adipose tissues of the CA-fed rats. Immunoglobulin A concentration in the ileal mucosa was elevated in the CA-fed rats and was correlated with the ileal adiponectin concentration. 12αOH BAs may modulate mucosal immune response that are involved in the accumulation of adiponectin in the ileum.

Adropin Slightly Modulates Lipolysis, Lipogenesis and Expression of Adipokines but Not Glucose Uptake in Rodent Adipocytes.

Adropin is a peptide hormone which modulates energy homeostasis and metabolism. In animals with diet-induced obesity, adropin attenuates adiposity and improves lipid and glucose homeostasis. Adropin promotes the proliferation of rodent white preadipocytes and suppresses their differentiation into adipocytes. By contrast, the effects of adropin on mature white adipocytes are unknown. Therefore, we aimed to evaluate the effects of adropin on lipolysis, lipogenesis and glucose uptake in white rodent adipocytes. We assessed the effects of adropin on the mRNA expression of adiponectin, resistin and visfatin. White preadipocytes were isolated from male Wistar rats. Differentiated 3T3-L1 cells were used as a surrogate model of white adipocytes. Lipolysis was measured by the evaluation of glycerol and free fatty acid secretion using colorimetric kits. The effects of adropin on lipogenesis and glucose uptake were measured using radioactive-labelled glucose. The expression of adipokine mRNA was studied using real-time PCR. Our results show that adropin slightly promotes lipolysis in rat adipocytes and 3T3-L1 cells. Adropin suppresses lipogenesis in rat adipocytes without influencing glucose uptake. In addition, adropin stimulates adiponectin mRNA expression and suppresses the expression of resistin and visfatin. These results indicate that adropin may be involved in controlling lipid metabolism and adipokine expression in white rodent adipocytes.