Adiponectin mRNA Research Articles

Citrulline counteracts overweight- and aging-related effects on adiponectin and leptin gene expression in rat white adipose tissue

We recently demonstrated that citrulline (CIT) reduced the expression of inflammatory genes in cultured explants from retroperitoneal (RET) white adipose tissue (WAT) from young (2–4 months) but not old (25 months) rats. Here we show that in RET WAT from old rats and high-fat-diet-fed (HFD) young rats, the basal expression of the leptin gene was increased (275–345%) whereas that of the adiponectin gene was decreased (48–60%), when compared to those from control-diet-fed (CD) young rats. We show also that in RET WAT from old rats, a diet supplemented with CIT for 3 months reduced macrophage (F4/80, CD68) and inflammation (interleukin-6, tumor necrosis factor-α) marker genes 23–97%. CIT supplementation lowered leptin mRNA 62% and increased adiponectin mRNA 232%. In cultured explants of RET WAT from 4 month-old CD, 4 month-old HFD and 25-month-old CD rats, the exposure to 2.5 mmol/L CIT for 24 h up-regulated adiponectin gene expression 151%, 362% and 216% respectively. In contrast, leptin gene expression was down-regulated 66% selectively in CIT-treated explants from 25-month-old CD rats. These results further support the proposed beneficial effect of CIT to counteract the deleterious effects of aging and overweight on the metabolic, inflammatory and endocrine functions of WAT.

The Anti-Inflammatory Effects of Lion's Mane Culinary-Medicinal Mushroom, Hericium erinaceus (Higher Basidiomycetes) in a Coculture System of 3T3-L1 Adipocytes and RAW264 Macrophages

Chronic low-grade inflammation in the adipose tissue accompanying obesity is thought to be an underlying driver of metabolic diseases. In this study, we aimed to investigate the efficacy of Hericium erinaceus on adipose tissue inflammation. The anti-inflammatory effects of the ethyl acetate soluble fraction of H. erinaceus (EAHE) were examined using cocultures of 3T3-L1 adipocytes and RAW264 macrophages. EAHE significantly suppressed tumor necrosis factor (TNF)-α and interleukin (IL)-6 production in cultured RAW264 macrophages stimulated by lipopolysaccharide (LPS). EAHE also caused notable inhibition of c-Jun N-terminal kinase (JNK) activation, which is thought to be involved in the suppression of proinflammatory cytokines by EAHE. In a coculture system with 3T3-L1 and RAW264 cells stimulated with LPS, EAHE reduced TNF-α and IL-6 concentrations in the conditioned medium and lowered the gene expression levels of these cytokines in 3T3-L1 adipocytes. Furthermore, EAHE suppressed the LPS-induced reduction of adiponectin mRNA levels in 3T3-L1 adipocytes cocultured with RAW264 macrophages. However, in 3T3-L1 adipocytes cultured alone, the concentration of LPS used in this study did not affect the gene expression levels of these adipokines. We attributed the anti-inflammatory effects of EAHE on 3T3-L1 adipocytes cocultured with RAW264 macrophages to the suppression of Toll-like receptor 4 (TLR4) signaling and subsequent proinflammatory cytokine secretion in RAW264 cells. Our findings indicate the possibility that H. erinaceus exerts anti-inflammatory effects on macrophages through the inhibition of TLR4-JNK signaling and prevents or ameliorates adipose tissue inflammation associated with obesity.

Polysaccharides from Enteromorpha prolifera Improve Glucose Metabolism in Diabetic Rats.

This study investigated the effects of polysaccharides from Enteromorpha prolifera (PEP) on glucose metabolism in a rat model of diabetes mellitus (DM). PEP (0, 150, 300, and 600 mg/kg) was administered intragastrically to rats for four weeks. After treatment, fasting blood glucose (FBG) and insulin (INS) levels were measured, and the insulin sensitivity index (ISI) was calculated. The morphopathological changes in the pancreas were observed. Serum samples were collected to measure the oxidant-antioxidant status. The mRNA expression levels of glucokinase (GCK) and insulin receptor (InsR) in liver tissue and glucose transporter type 4 (GLUT-4) and adiponectin (APN) in adipose tissue were determined. Compared with the model group, the FBG and INS levels were lower, the ISI was higher, and the number of islet β-cells was significantly increased in all the PEP groups. In the medium- and high-dose PEP groups, MDA levels decreased, and the enzymatic activities of SOD and GSH-Px increased. The mRNA expression of InsR and GCK increased in all the PEP groups; APN mRNA expression increased in the high-dose PEP group, and GLUT-4 mRNA expression increased in adipose tissue. These findings suggest that PEP is a potential therapeutic agent that can be utilized to treat DM.

Abstract 18391: Accumulation of Adiponectin in Association With Up-regulated T-cadherin in the Aortic Wall of Acute and Chronic Aortic Dissection

Introduction: Adiponectin (APN) is a major adipokine, which has been reported to accumulate into the damaged tissues in multiple organs. However, the role of APN and its receptor, T-cadherin (T-cad), in the pathology of the human aortic wall (AW) is poorly understood. In this study, we examined the distributions of APN and T-cad in the dissected AW and measured the serum APN concentration in patients with aortic dissection (AD). Methods: Diseased AW tissues were collected from patients with acute or chronic AD at the time of surgery, and a healthy aorta was used as a control (n = 6 per group). Blood was serially sampled to measure the APN concentrations in non-surgically-treated patients with acute type B AD (n = 10). Results: Immunohistochemically, normal aortic walls weakly expressed APN or T-cad on the intimal surface, whereas the AWs of acute AD patients showed marked expression of both APN and T-cad on the surface of the dissected aortic media. In chronic AD, APN and T-cad were diffusely expressed on the medial layers of the thickened AW (Fig. A-C). Western blot analysis showed that APN expression in the AW was significantly greater in acute and chronic AD than in the normal aorta (151 ± 2% and 220 ± 27% vs. normal, respectively) (Fig. D). RT-PCR revealed no expression of APN mRNA in any AW, and stronger expression of T-cad mRNA in acute and chronic AD than in the normal aorta (108 ± 9% and 194 ± 101% vs. normal, respectively). The blood concentration of APN in type B AD patients decreased by 13.3 ± 3.8% in 24-78 hours, and by 22.7 ± 7.2% in over 78 hours, as compared to those monitored within 24 hours after the onset, indicating that APN was supplied to the affected aortic wall from the blood. Conclusions: APN markedly accumulated into the dissected aortic media in acute and chronic AD, and T-cad was upregulated in the corresponding area. In contrast, the blood concentration of APN reciprocally decreased after AD onset, indicating a possibility of APN contribution to protect a diseased aortic wall of AD.

MicroRNA-378 regulates adiponectin expression in adipose tissue: a new plausible mechanism.

AimsMechanisms regulating adiponectin expression have not been fully clarified. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, are involved in biological processes, including obesity and insulin resistance. We evaluated whether the miRNA-378 pathway is involved in regulating adiponectin expression.Methods and ResultsFirst, we determined a putative target site for miRNA-378 in the 3 prime untranslated region (3'UTR) of the adiponectin gene by in silico analysis. The levels of adiponectin mRNA and protein were decreased in 3T3-L1 cells overexpressing the mimic of miRNA-378. Luminescence activity in HEK293T cells expressing a renilla-luciferase-adiponectin-3'UTR sequence was inhibited by overexpressing the mimic of miRNA-378, and the decrease was reversed by adding the inhibitor of miRNA-378. Moreover, we confirmed the inhibitory effects of the mimic were cancelled in a deleted mutant of the miR-378 3′-UTR binding site. Addition of tumor necrosis factor-α (TNFα) led a upregulation of miR-378 and downregulation of adiponectin at mRNA and protein levels in 3T3-L1 cells. Level of miR-378 was higher and mRNA level of adiponectin was lower in diabetic ob/ob mice than those of normal C57BL/6 mice and levels of miR378 and adiponectin were negatively well correlated (r = −0.624, p = 0.004).ConclusionsWe found that levels of miRNA-378 could modulate adiponectin expression via the 3'UTR sequence-binding site. Our findings warrant further investigations into the role of miRNAs in regulating the adiponectin expression.

Involvement of adiponectin in early stage of colorectal carcinogenesis.

BackgroundAlthough altered levels of adiponectin have been reported as a potential risk factor in colorectal cancer (CRC), the importance of the role played by adiponectin in colorectal carcinogenesis has not been established. We sought to examine the expression pattern of adiponectin and adiponectin receptors (AdipoRs) in the normal-adenoma-carcinoma sequence and to assess the implications of adiponectin in colorectal carcinogenesis.MethodsSerum adiponectin concentrations, and the mRNA and protein expression of adiponectin and AdipoRs were examined using serum and tissues from patients with CRC, advanced adenoma, and a normal colon. mRNA expression of AdipoRs and epithelial-mesenchymal transition regulators including E-cadherin, cyclooxygenase-2 (COX-2) and T-cadherin were examined in HCT116 cells treated with adiponectin.ResultsSerum adiponectin concentrations in patients with advanced adenoma and CRC were lower than those in controls. Adiponectin mRNA was not detected in colonic tissue, whereas AdipoRs mRNA was lower in advanced adenoma and CRC than that in normal colon tissues. Immunohistochemical staining demonstrated that adiponectin was expressed in spindle-shaped cells of the subepithelial layer in normal colon tissues, whereas ill-defined overexpression of adiponectin was seen in the stroma of advanced adenoma and CRC tissues. AdipoRs expression was strong in normal epithelium, but weak to negative in the epithelia of CRC tissues. Adiponectin downregulated COX-2 mRNA expression in vitro, but upregulated T-cadherin in HCT116 cells.ConclusionsSystemic adiponectin and local AdipoRs expression in the colon may be associated with anti-tumorigenesis during the early stages of CRC. These findings offer new insight into understanding the relationship between adiponectin and colorectal carcinogenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-811) contains supplementary material, which is available to authorized users.

Abstract 256: AMP-activated Protein Kinase Activator AICAR Attenuates TNFα-induced Inflammation In Murine Adipocytes.

Adipose tissue, a metabolically active tissue and important regulator of vascular function, contributes to obesity-related cardiovascular diseases such as hypertension. Molecular mechanisms are still elusive, but inflammation and activation of a local renin-angiotensin-aldosterone system (RAAS) seem to play an important role in adipocyte dysfunction leading to vascular damage. AMP-activated protein kinase (AMPK), a key regulator of cell metabolism, may play an important role in adipose tissue biology/inflammation. In this study, we evaluated whether AMPK activation regulates TNFα-induced inflammation and RAAS status in adipocytes. Murine adipocytes (3T3-L1) were used and treated with 10ng/ml TNFα in the absence/presence of AICAR (1mM - AMPK activator). Pro-inflammatory markers were assessed by qPCR or ELISA and protein expression by immunoblotting. TNFα stimulation increased IL-6 (113.4 fold) and MCP-1 (449.6 fold) mRNA levels, as well as IL-6 release (17.67 fold) into culture medium (p<0.05, vs vehicle); an effect abrogated by AICAR (75% reduction MCP-1 mRNA, 60% reduction IL-6 mRNA and 30% reduction IL-6 release). Adiponectin mRNA levels were decreased by TNFα (60%, p<0.05 vs vehicle), yet preincubation with AICAR had no effect. The effects of TNFα were also evaluated on components of the RAAS. TNFα induced a decrease in angiotensinogen (60%), mineralocorticoid receptor (70%) and AT2R (90%) mRNA levels in adipocytes (p<0.05), which was unaffected by AICAR. Activation of AMPK also suppressed TNFα-stimulated phosphorylation of MAP kinases and NFκB assessed by immunoblotting. In conclusion, AMPK activation seems to play a role in the control of inflammation and RAAS in adipocytes. Our data highlights the importance of AMPK as an important anti-inflammatory signaling protein in adipose tissue and may be an interesting target for treatment of obesity-related vascular injury leading to hypertension. This is especially significant given that the commonly used drug metformin is an AMPK inhibitor.

Macrophages Inhibit Insulin Signalling in Adipocytes: Role of Inducible Nitric Oxide Synthase and Nitric Oxide

The interaction of immune cells with adipocytes within the adipose tissues in obese persons with diabetes mellitus may play a role in insulin resistance. We examined invitro whether nitric oxide (NO) and inducible nitric oxide synthase (iNOS) play a role in impaired insulin signalling in adipocytes exposed to activated macrophages. We used a co-culture system in which Raw264.7 macrophages were plated over differentiated, low passage 3T3-L1 cells (dif3T3) at a cell density ratio of 1:2. Inflammation was induced by a challenge with bacterial lipopolysaccharide. Significantly (p<0.001) enhanced iNOS expression and NO synthesis was observed in activated co-cultures. In the co-cultures as compared with Raw264.7 cells alone, iNOS protein was induced up to 11-fold above background, and NO release was significantly (p<0.001) increased up to 2.8-fold. Co-culturing dif3T3 and Raw264.7 cells as compared to dif3T3 alone reduced insulin-induced Akt phosphorylation by 50% and AS160 phosphorylation by 42%. This was correlated with reduced glucose consumption when dif3T3 was exposed to 1,3-morpholinosydnonimine. Adiponectin, GLUT4 and AS160 mRNA were reduced by 4-fold, 5-fold and 2-fold, respectively, in co-cultures as compared to dif3T3 alone. On the contrary, GLUT1 mRNA levels were increased by 2-fold in co-cultures as compared to dif3T3. NG-monomethyl-L-arginine abolished NO production with modest reversal of Akt/AS160 phosphorylation. This study demonstrated a potential association between iNOS/NO-mediated inflammation and insulin resistance.

생쥐 지방조직에서의 아디포넥틴과 포도당수송체-4 유전자 발현의 상관관계

Adiponectin has been known to improve insulin sensitivity and elicit glucose uptake via increased glucose transporter 4 (GLUT4) translocation. In the current study, mRNA expression levels of adiponectin and GLUT4 were measured in subcutaneous adipose tissue from C57BL/6 mice fed normal (ND) or high-fat diet (HFD) until 16, 26, 36, 47, or 77 weeks of age starting from 6 weeks of age. Expression levels were also measured in mice with calorie restriction (CR) and in thiazolidinedione (TZD) treated mice. Using quantitative real-time PCR, we demonstrated that GLUT4 expression in adipose tissue significantly decreased in HFD mice groups and increased in CR (p<0.05) and TZD (p=0.007) groups while there was no difference in adiponectin mRNA expression levels between experimental and control groups. General linear regression models were used to assess the association of gene expression levels between adiponectin and GLUT4 and to determine whether adiponectin affects GLUT4 transcription. mRNA expression levels of adiponectin and GLUT4 are significantly associated each other in mice fed a ND (p<0.0001) or HFD (p<0.0001), in groups separated into each age and diet, and CR group (p=0.002), but not in TZD group (p=0.73). These results demonstrated that gene expression of adiponectin and GLUT4 is strongly associated, suggesting that there is a common regulatory mechanism for adiponectin and GLUT4 gene expression and/or adiponectin has a direct role in GLUT4 gene expression in adipose tissue.

DNA aptamer raised against advanced glycation end products (AGEs) improves glycemic control and decreases adipocyte size in fructose-fed rats by suppressing AGE-RAGE axis.

Advanced glycation end products (AGEs) decrease adiponectin expression and suppress insulin signaling in cultured adipocytes through the interaction with a receptor for AGEs (RAGE) via oxidative stress generation. We have recently found that high-affinity DNA aptamer directed against AGE (AGE-aptamer) prevents the progression of experimental diabetic nephropathy by blocking the harmful actions of AGEs in the kidney. This study examined the effects of AGE-aptamer on adipocyte remodeling, AGE-RAGE-oxidative stress axis, and adiponectin expression in fructose-fed rats. Although AGE-aptamer treatment by an osmotic mini pump for 8 weeks did not affect serum insulin levels, it significantly decreased average fasting blood glucose and had a tendency to inhibit body weight gain in fructose-fed rats. Furthermore, AGE-aptamer significantly suppressed the increase in adipocyte size and prevented the elevation in AGEs, RAGE, and an oxidative stress marker, 8-hydroxydeoxyguanosine (8-OHdG), levels in adipose tissues of fructose-fed rats at 14-week-old, while it restored the decrease in adiponectin mRNA levels. Our present study suggests that AGE-aptamer could improve glycemic control and prevent adipocyte remodeling in fructose-fed rats partly by suppressing the AGE-RAGE-mediated oxidative stress generation. AGE-aptamer might be a novel therapeutic strategy for fructose-induced metabolic derangements.

Dexamethasone treatment alters function of adipocytes from a mesenchymal stromal cell line

Osteoporosis and osteonecrosis are associated with corticosteroid treatment, but the pathophysiologies are unclear. We hypothesized that mature adipocytes present within the bone marrow compartment play a key role in the development of both diseases. Adipocytes have recognized regulatory effects on bone viability and healing by releasing signaling molecules called adipokines. Our purpose was to evaluate whether dexamethasone alters adipokine expression in differentiated bone-marrow-derived adipocytes. Adipocytes differentiated from mouse D1 mesenchymal stromal cells were treated with dexamethasone (10−5, 10−6, 10−7, or 10−8M) or with diluent alone (controls) for up to 6days. Using real-time polymerase chain reaction and enzyme-linked immunosorbent assay analyses, six key adipokines and the transcription factor HIF-1α were evaluated. Dexamethasone treatment increased PAI-1 protein expression with increased mRNA expression at 4days, while decreasing HIF-1α mRNA expression and protein concentrations. VEGF A mRNA expression was increased at 4days for most dexamethasone concentrations, with minimal changes in protein levels. Dexamethasone increased adiponectin mRNA expression and protein levels at 4 and 6days and decreased leptin, interleukin-6, and tumor necrosis factor α mRNA expression at all time periods. Dexamethasone treatment of bone-marrow-derived adipocytes resulted in detectable changes in mRNA expression and protein levels of adipokines and HIF-1α. The detected adipokine alterations could be important early events in the pathogenesis of steroid-induced osteonecrosis and osteoporosis.

Placental miR-1301 is dysregulated in early-onset preeclampsia and inversely correlated with maternal circulating leptin

IntroductionmiRNAs are small non-coding RNAs important for the regulation of mRNA in many organs including placenta. Adipokines and specifically leptin are known to be dysregulated in preeclampsia, but little is known regarding their regulation by miRNAs during pregnancy. MethodsWe performed high-throughput sequencing of small RNAs in placenta from 72 well-defined patients: 23 early-onset preeclampsia (PE), 26 late-onset PE and 23 controls. The regulation of some miRNAs was confirmed on qRT-PCR. Maternal circulating levels and placental mRNA of leptin, resistin and adiponectin were measured using Bio-Plex and qRT-PCR. ResultsWe found that miR-1301, miR-223 and miR-224 expression was downregulated in early-onset PE, but not in late-onset PE, compared to controls. In silico analysis predicted the leptin gene (LEP) to be a target for all three miRNAs. Indeed, we found significant correlation between maternal circulating levels of leptin and placental LEP expression. In addition, we found a significant inverse correlation between maternal circulating leptin/placental LEP expression and placental miR-1301 expression levels. Interestingly, placental expression of miR-1301 was also correlated with newborn weight percentile and inversely correlated with both maternal systolic and diastolic blood pressure prior to delivery. DiscussionOur results confirm that placenta is a major site of LEP expression during pregnancy. It further suggests that miR-1301 could be involved in the regulation of leptin during pregnancy and may play a role in early-onset PE. ConclusionsmiR-1301 is dysregulated in early-onset preeclampsia and could possibly play a role in the regulation of leptin during pregnancy.

Juvenile obesity aggravates disease severity in a rat model of atopic dermatitis.

PurposeThere is increasing epidemiological evidence of an association between childhood obesity and atopic dermatitis, but little is known about the underlying mechanism(s). In the present study, we used a rat model of atopic dermatitis to assess whether juvenile obesity, induced by reduction of litter size, aggravated the signs of atopic dermatitis and, if so, whether this aggravation was associated with changes in plasma concentration of adipokines, such as leptin and adiponectin.MethodsDermatitis was induced by neonatal capsaicin treatment. Body weight, dermatitis score, serum IgE, skin nerve growth factor (NGF), serum leptin and adiponectin, and cytokine mRNA expression in the skin lesion were compared between small (SL, 5 pups) and large litters (LL, 15 pups).ResultsThe body weight of juvenile rats up to 6 weeks of age was significantly heavier in the SL group, compared with those in the LL group. The SL group showed more robust development of dermatitis, and higher levels of serum IgE and skin NGF than the LL group. Additionally, the SL group demonstrated higher levels of leptin and pro-inflammatory cytokine mRNA but lower levels of adiponectin than the LL group.ConclusionsThese results suggest a causal link between a decrease in immunological tolerance, induced by juvenile obesity, and aggravation of atopic dermatitis.

Reactive oxygen species up-regulates SOCS-3 in 3T3-L1 adipocytes

We investigated the effect of increased intracellular reactive oxygen species(ROS) on SOCS-3 expression in 3T3-L1 adipocytes. Increased intracellular ROS levels in 3T3-L1 adipocytes were achieved by two methods of exposure to H2O2 and the occurrence of oxidative stress in cells was assessed by flow cytometry . Expression of SOCS-3 mRNA and that of some adipokines were measured by real time PCR. The level of SOCS-3 protein was determined by western blot. The effect of the antioxidant alpha-lipoic acid was also investigated. Both the relatively mild increased intracellular ROS and the acute but transient increased ROS elevated the levels of SOCS-3 mRNA and protein in 3T3-L1 adipocytes, acompanied with elevated levels of TNF-α mRNA and resistin mRNA and the decreased levels of adiponectin mRNA and secretory adiponectin in culture medium. α-lipoic acid could attenuate the effects of ROS on 3T3-L1 adipocytes. We hypothesized that in mature 3T3-L1 adipocytes, SOCS-3 could be upregulated directly by the induction of increased intracellular ROS and to some extent which was up-regulated by adipokine modulation.

Positive regulations of adipogenesis by Italian ryegrass [Lolium multiflorum] in 3T3-L1 cells.

Back groundIntramuscular fat deposition in the meat animal is relatively new strategy for developing the meat quality. Fat deposition is largely depending on the adipocyte proliferation and differentiation. Therefore, we investigated the effect of chloroform extract of L. multiflorum [CELM] on cell proliferation, lipid accumulation and adipocyte differentiation in 3T3-L1 cells and body weight of mouse.ResultsWe identified 6,9-Octadecatrienoic acid, Hexadecanoic acid, 2-hydroxypropanoic acid, butane-2,3-diol and hexane-1,2,3,4,5,6-hexaol in CELM. L. multiflorum extract increased the cell viability, lipid accumulation, cell cycle progression and key transcriptional and secretory factors like PPRAγ2, C/CEBP-α, adiponectin, aP2, GLUT-4, FAS and SREBP-1 mRNA expression as compared with control cells. For in-vivo, mice administered with CELM significantly increased body weight throughout the experiment periods. Further, the identified fatty acids like 3, 6, 9-Octadecatrienoic acid and Hexadecanoic acid was docked with target protein [PPRAγ2] using HEX 6.12. The least binding energy considered as high affinity with target protein. The maximum affinity with the target protein was observed in the Hexadecanoic acid followed by 3, 6, 9-Octadecatrienoic acid. The binding efficacy of Hexadecanoic acid and 3, 6, 9-Octadecatrienoic acid to the active site of PPAR-γ2 may be enhanced the adipocyte differentiations.ConclusionThese findings suggest that CELM stimulates adipogenesis via activating the PPARγ-mediated signaling pathway in adipocyte which could be useful for the development of meat quality in animals.

Ultraviolet B irradiation reduces the expression of adiponectin in ovarial adipose tissues through endocrine actions of calcitonin gene-related peptide-induced serum amyloid A.

Ultraviolet (UV) B irradiation decreases blood adiponectin levels, but the mechanism is not well understood. This study investigated how UVB irradiation reduces adiponectin expression in ovarial adipose tissues. Female Hos:HR-1 hairless mice were exposed to UVB (1.6 J/cm2) irradiation and were killed 24 h later. UVB irradiation decreased the adiponectin protein level in the serum and the adiponectin mRNA level in ovarial adipose tissues. UVB irradiation also decreased the mRNA levels of peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer binding protein (C/EBP) α, C/EBPβ, and fatty acid binding protein 4 (aP2) in ovarial adipose tissues. In contrast, UVB irradiation increased the mRNA levels of interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1 in ovarial adipose tissues. In the serum and liver, the levels of serum amyloid A (SAA), involved in PPARγ, C/EBPα, C/EBPβ, aP2, IL-6, and MCP-1 regulation, increased after UVB irradiation. The SAA gene is regulated by IL-1β, IL-6, and tumor necrosis factor-α, but only IL-6 expression increased in the liver after UVB irradiation. Additionally, in the liver, hypothalamus, and epidermis, UVB irradiation increased the expression of calcitonin gene-related peptide (CGRP), which upregulates SAA in the liver. Collectively, our results suggest that the CGRP signal induced by skin exposure to UVB transfers to the liver, possibly through the brain, and increases SAA production via IL-6 in the liver. In turn, serum SAA acts in an endocrine manner to decreases the serum adiponectin level by downregulating factors that regulate adiponectin expression in adipose tissues.

Substitution of soy protein for casein prevents oxidative modification and inflammatory response induced in rats fed high fructose diet.

Fructose-rich diet is known to cause metabolic dysregulation, oxidative stress, and inflammation. We aimed to compare the effects of two dietary proteins of animal and plant origins on fructose-induced oxidative stress and inflammatory changes in liver. Wistar rats were fed either starch or fructose (60%) diet with casein or soy protein (20%) as the protein source for 8 weeks. Glucose and insulin, glycated hemoglobin and fructosamine, AOPP, and FRAP were determined in circulation. Intracellular ROS, oxidatively modified proteins (4-HNE and 3-NT adducts), adiponectin, TNF-α, IL-6 and PAI-1 mRNA expression, phosphorylation and activation of JNK and IKKβ, and NF-κB binding activity were assayed in liver. In comparison with starch fed group, fructose + casein group registered significant decline in antioxidant potential and increase in plasma glucose, insulin, and glycated proteins. Increased ROS production, 4-HNE and 3-NT modified proteins, JNK and IKKβ activation, and NF-κB binding activity were observed in them along with increased gene expression of PAI-1, IL-6, and TNF-α and decreased adiponectin expression. Substitution of soy protein for casein reduced oxidative modification and inflammatory changes in fructose-fed rats. These data suggest that soy protein but not casein can avert the adverse effects elicited by chronic consumption of fructose.

Maternal high folic acid supplement promotes glucose intolerance and insulin resistance in male mouse offspring fed a high-fat diet.

Maternal nutrition may influence metabolic profiles in offspring. We aimed to investigate the effect of maternal folic acid supplement on glucose metabolism in mouse offspring fed a high-fat diet (HFD). Sixty C57BL/6 female mice were randomly assigned into three dietary groups and fed the AIN-93G diet containing 2 (control), 5 (recommended folic acid supplement, RFolS) or 40 (high folic acid supplement, HFolS) mg folic acid/kg of diet. All male offspring were fed HFD for eight weeks. Physiological, biochemical and genetic variables were measured. Before HFD feeding, developmental variables and metabolic profiles were comparable among each offspring group. However, after eight weeks of HFD feeding, the offspring of HFolS dams (Off-HFolS) were more vulnerable to suffer from obesity (p = 0.009), glucose intolerance (p < 0.001) and insulin resistance (p < 0.001), compared with the controls. Off-HFolS had reduced serum adiponectin concentration, accompanied with decreased adiponectin mRNA level but increased global DNA methylation level in white adipose tissue. In conclusion, our results suggest maternal HFolS exacerbates the detrimental effect of HFD on glucose intolerance and insulin resistance in male offspring, implying that HFolS during pregnancy should be adopted cautiously in the general population of pregnant women to avoid potential deleterious effect on the metabolic diseases in their offspring.

Vagal Hyperactivity Due to Ventromedial Hypothalamic Lesions Increases Adiponectin Production and Release

In obese humans and animals, adiponectin production and release in adipose tissue are downregulated by feedback inhibition, resulting in decreased serum adiponectin. We investigated adiponectin production and release in ventromedial hypothalamic (VMH)-lesioned animals. VMH-lesioned mice showed significant increases in food intake and body weight gain, with hyperinsulinemia and hyperleptinemia at 1 and 4 weeks after VMH-lesioning. Serum adiponectin was elevated in VMH-lesioned mice at 1 and 4 weeks, despite adipocyte hypertrophy in subcutaneous and visceral adipose tissues and increased body fat. Adiponectin production and mRNA were also increased in both adipose tissues in VMH-lesioned mice at 1 week. These results were replicated in VMH-lesioned rats at 1 week. Daily atropine administration for 5 days or subdiaphragmatic vagotomy completely reversed the body weight gain and eliminated the increased adiponectin production and release in these rats, with reversal to a normal serum adiponectin level. Parasympathetic nerve activation by carbachol infusion for 5 days in rats increased serum adiponectin, with increased adiponectin production in visceral and subcutaneous adipose tissues without changes of body weight. These results demonstrate that activation of the parasympathetic nerve by VMH lesions stimulates production of adiponectin in visceral and subcutaneous adipose tissues and adiponectin release, resulting in elevated serum adiponectin.

Effect of Coculturing on the Myogenic and Adipogenic Marker Gene Expression

The present experiment was carried out to evaluate the effect of coculturing on myogenic and adipogenic marker gene expressions with the use of C2C12 and 3 T3-L1 preadipocyte cells under the coculture system. C2C12 and 3 T3-L1 cells were cocultured using transwell inserts with a 0.4-μm porous membrane to separate C2C12 and 3 T3-L1 cells. Each cell type was grown independently on the transwell plates. Following cell differentiation, inserts containing 3 T3-L1 cells were transferred to C2C12 plates, and inserts containing C2C12 cells were transferred to 3 T3-L1 plates. After coculture of the C2C12 and 3 T3-L1 cells for 48 and 72 h, the cells in the lower well were harvested for analysis, and this process was carried out for both cells. Myogenic markers such as myogenin, MyoD, Myf5, PAX3, and PAX7 mRNA expressions were analyzed in the cocultured C2C12 cells. Adipogenic markers such as fatty acid-binding protein 4 (FABP4), peroxisome proliferator-activating receptor (PPARγ), CCAAT/enhancer-binding protein (CEBPA), adiponectin, lipoprotein lipase, and fatty acid synthase mRNA expressions were analyzed in the cocultured 3 T3-L1 cells. Myogenic and adipogenic marker gene mRNA expressions were significantly altered in the cocultured C2C12 and 3 T3-L1 cells when compared with the monocultured C2C12 and 3 T3-L1 cells.