Peroxisome Proliferator-activated Receptor Gamma Gene Research Articles

Alternative Transcription of Peroxisome Proliferator-Activated Receptor Gamma in the Liver Is Associated with Fatness of Chickens

ABSTRACT The expression of four transcription variant of peroxisome proliferator-activated receptor gamma gene (PPARG) (XM_015292931.1; XM_015292932.1; XM_015292933.1 and NM_001001460.1) in the liver of broilers was measured and its correlation with abdominal fat weight and relative abdominal fat content was investigated. The study was conducted with 92 slow-growing crossbred chickens (Cobb males x indigenous Green-legged Partridge female chickens) divided into “fat” and “lean” groups, according to their abdominal fat yield. The NM_001001460.1 transcriptwas upregulated with ratio of means 4.26 (p≤0.01) in the “fat” group in relation to the “lean” group. Expression of this transcript was highly correlated with relative abdominal fat content (0.71, p≤0.01) and abdominal fat weight (0.59, p≤0.01). Two SNPs are located in putative transcription factor binding sites. Mutation -991C>A disrupts PPAR while mutation -884C>T disrupts C/EBP putative binding site. The gene expression analysis of PPARg showed that the expression of the transcripts (NM_001001460.1) was more than four times higher in fat than in lean chickens. These results point out that the peroxisome proliferator-activated receptor gamma NM_001001460.1 transcript could be candidate gene for determination of abdominal fat deposition in the chickens.

Neuronal preservation and reactive gliosis attenuation following neonatal sciatic nerve axotomy by a fluorinated cannabidiol derivative

Immature peripheral nervous system damage, such as the transection of a peripheral nerve, results in the extensive degeneration of motoneurons and dorsal root ganglia (DRG) sensory neurons, mostly due to apoptotic events. We have previously shown that cannabidiol (CBD), the most abundant non-psychotropic molecule present in the Cannabis sativa plant, exhibits neuroprotective action when administered daily at a dose of 15 mg/kg. This study shows that use of the fluorinated synthetic version of CBD (4′-fluoro-cannabidiol, HUF-101) significantly improves neuronal survival by 2-fold compared to that achieved with traditional CBD at one-third the dose. Furthermore, we show that HUF-101 administration significantly upregulates anti-apoptotic genes and blocks the expression of pro-apoptotic nuclear factors. Two-day-old Wistar rats were subjected to unilateral sectioning of the sciatic nerve and treated daily with HUF-101 (1, 2.5, 5 mg/kg/day, i.p.) or a vehicle solution for five days. The results were evaluated by Nissl staining, immunohistochemistry, and qRT-PCR. Neuronal counting revealed a 47% rescue of spinal motoneurons and a 79% rescue of DRG neurons (HUF-101, 5 mg/kg). Survival was associated with complete depletion of p53 and a 60-fold elevation in BCL2-like 1 gene expression. Additionally, peroxisome proliferator-activated receptor gamma (PPAR-gamma) gene expression was downregulated by 80%. Neuronal preservation was coupled with a high preservation of synaptic coverage and a reduction in astroglial and microglial reactions that were evaluated in nearby spinal motoneurons present in the ventral horn of the lumbar intumescence. Overall, these data strongly indicate that HUF-101 exerts potent neuroprotective effects that are related to anti-apoptotic protection and the reduction of glial reactivity.

The PPARG Pro12Ala Polymorphism and 20-year Cognitive Decline: Race and Sex Heterogeneity.

Previous reports suggest race/ethnic and sex heterogeneity in the association between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma (PPARG) gene and cognitive decline. Tests of verbal memory, processing speed, and verbal fluency and a composite global Z-score were used to assess cognitive performance longitudinally in a large (n=11,620) biracial cohort of older adults in the Atherosclerosis Risk in Communities Neurocognitive Study from midlife to older age. Linear mixed models were used to estimate associations between the Ala12 allele and cognitive performance over 20 years of follow-up. Heterogeneity was present for rate of cognitive decline as measured by the global Z-score by race, sex, and Ala12 allele status (P=0.01 for 4-way interaction term: race×sex×time×Ala12 carrier status). Stratified analysis showed a significantly increased rate of global cognitive decline over the 20-year follow-up for carriers of the Ala12 allele compared with noncarriers among black male individuals (-0.92 SD decline vs. -0.57 SD; P=0.02) but not among black female, white male, or white female individuals. Decline in global cognitive function among black male Ala12 carriers was primarily driven by decline in verbal memory. Our data underscore the context-dependent association between the Pro12Ala polymorphism and cognitive decline, specifically race/ethnic background and sex.

Fibroblast growth factor receptor 3 (FGFR3), peroxisome proliferator-activated receptor gamma (PPARg), and outcomes with nivolumab (nivo) in metastatic urothelial cancer (UC).

511 Background: Prior studies have correlated FGFR3 mutations (mut) and increased PPARg expression with decreased T-cell infiltration raising the possibility that these might represent mediators of PD-1/PD-L1 blockade resistance in luminal UC and targets for combination strategies. The causality of these associations remains unclear and the clinical relevance in PD-1/PD-L1 blockade treated patients has been underexplored. Methods: Archival tumor specimens from patients enrolled on CheckMate 275, a phase 2 trial of nivo in patients with platinum-resistant metastatic UC, underwent whole exome sequencing (WES) and gene expression profiling (HTG EdgeSeq). CD8 expression was determined by immunohistochemistry. Results: WES and gene expression data was available for 139 and 217 patients, respectively; the baseline characteristics and outcomes of both cohorts were similar to the full CheckMate 275 cohort. FGFR3mut were detected in 15 patients (11%) and correlated with higher FGFR3 gene expression. Neither FGFR3mut nor FGFR gene expression correlated with CD8 expression (Pearson's r -0.13; p=0.16) or with response rate (RR), progression-free survival (PFS), or overall survival (OS); RR in FGFRmut vs. FGFRwt = 20% vs 20%. PPARg gene expression was inversely correlated with CD8 (Pearson’s r -0.44; P <0.001) and IFNg gene expression (Pearson’s r -0.52; P <0.001). Higher PPARg gene expression was associated with inferior outcomes (Table); RR in PPARg highest vs lowest tertile = 15% vs 24%. Conclusions: FGFR3 alterations (mut/increased expression) do not preclude response to nivo and were not associated with decreased CD8. Higher PPARg expression was associated with decreased CD8, lower RR to nivo, and significantly shorter PFS and OS. These data support exploring therapeutic modulation of PPARg or downstream mediators in an effort to overcome resistance to PD-1/PD-L1 blockade. Cox proportional hazards model. [Table: see text]

Long-chain polyunsaturated fatty acids and extensively hydrolyzed casein-induced browning in a Ucp-1 reporter mouse model of obesity.

Browning in adipose tissues, which can be affected by diet, may mitigate the detrimental effects of adiposity and improve longer-term metabolic health. Here, browning-inducing effects of long-chain polyunsaturated fatty acids, e.g., arachidonic acid (ARA)/docosahexaenoic acid (DHA) and extensively hydrolyzed casein (eHC) were investigated in uncoupling protein 1 (Ucp-1) reporter mice. To address the overall functionality, their potential role in supporting a healthy metabolic profile under obesogenic dietary challenges later in life was evaluated. At weaning Ucp1+/LUC reporter mice were fed a control low fat diet (LFD) with or without ARA + DHA, eHC or eHC + ARA + DHA for 8 weeks until week 12 after which interventions continued for another 12 weeks under a high-fat diet (HFD) challenge. Serology (metabolic responses and inflammation) and in vivo and ex vivo luciferase activity were determined; in the meantime browning-related proteins UCP-1 and the genes peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), PR domain containing 16 (PRDM16) and Ucp-1 were examined. ARA + DHA, eHC or their combination reduced body weight gain and adipose tissue weight compared to the HFD mice. The interventions induced Ucp-1 expression in adipose tissues prior to and during the HFD exposure. Ucp-1 induction was accompanied by higher PGC1a and PRDM16 expression. Glucose tolerance and insulin sensitivity were improved coinciding with lower serum cholesterol, triglycerides, free fatty acids, insulin, leptin, resistin, fibroblast growth factor 21, alanine aminotransferase, aspartate aminotransferase and higher adiponectin than the HFD group. HFD-associated increased systemic (IL-1β and TNF-α) and adipose tissue inflammation (F4/80, IL-1β, TNF-α, IL-6) was reduced. Studies in a Ucp-1 reporter mouse model revealed that early intervention with ARA/DHA and eHC improves metabolic flexibility and attenuates obesity during HFD challenge later in life. Increased browning is suggested as, at least, part of the underlying mechanism.

Adipogenic genes expression in relation to hepatic steatosis in the liver of two duck species

Some studies have shown that expression of peroxisome proliferator-activated receptor gamma (PPARG), a key regulator of adipogenesis, and of some adipocyte-specific genes or adipokines are expressed in hepatic steatosis, leading to the concept of ‘adipogenic hepatic steatosis’ or ‘hepatic adiposis.’ Most of these studies were conducted in genetic obese mouse models or after manipulation of gene expression. The relevance of this concept to other species and more physiological models was here addressed in ducks which are able to develop hepatic steatosis after overfeeding. The expression of PPARG and other adipocyte-specific genes was thus analyzed in the liver of ducks fed ad libitum or overfed and compared with those observed in adipose tissues. Pekin (Anas platyrhynchos) and Muscovy ducks (Cairina moschata) were analyzed, as metabolic responses to overfeeding differ according to these two species, Muscovy ducks having a greater ability to synthesize and store lipids in the liver than Pekin ducks. Our results indicate that adipocyte-specific genes are expressed in the liver of ducks, PPARG and fatty acid-binding protein 4 being upregulated and adiponectin and leptin receptor downregulated by overfeeding. However, these expression levels are much lower than those observed in adipose tissue suggesting that fatty liver cells are not transformed to adipocytes, although some hepato-specific functions are decreased in fatty liver when compared with normal liver.

Resveratrol inhibits obesity-associated adipose tissue dysfunction and tumor growth in a mouse model of postmenopausal claudin-low breast cancer.

Adipose tissue dysregulation, a hallmark of obesity, contributes to a chronic state of low-grade inflammation and is associated with increased risk and progression of several breast cancer subtypes, including claudin-low breast tumors. Unfortunately, mechanistic targets for breaking the links between obesity-associated adipose tissue dysfunction, inflammation, and claudin-low breast cancer growth have not been elucidated. Ovariectomized female C57BL/6 mice were randomized (n = 15/group) to receive a control diet, a diet-induced obesity (DIO) diet, or a DIO + resveratrol (0.5% wt/wt) diet. Mice consumed these diets ad libitum throughout study and after 6 weeks were orthotopically injected with M-Wnt murine mammary tumor cells, a model of estrogen receptor (ER)-negative claudin-low breast cancer. Compared with controls, DIO mice displayed adipose dysregulation and metabolic perturbations including increased mammary adipocyte size, cyclooxygenase-2 (COX-2) expression, inflammatory eicosanoid levels, macrophage infiltration, and prevalence of crown-like structures (CLS). DIO mice (relative to controls) also had increased systemic inflammatory cytokines and decreased adipocyte expression of peroxisome proliferator-activated receptor gamma (PPARγ) and other adipogenesis-regulating genes. Supplementing the DIO diet with resveratrol prevented obesity-associated increases in mammary tumor growth, mammary adipocyte hypertrophy, COX-2 expression, macrophage infiltration, CLS prevalence, and serum cytokines. Resveratrol also offset the obesity-associated downregulation of adipocyte PPARγ and other adipogenesis genes in DIO mice. Our findings suggest that resveratrol may inhibit obesity-associated inflammation and claudin-low breast cancer growth by inhibiting adipocyte hypertrophy and associated adipose tissue dysregulation that typically accompanies obesity.

Adipose Tissue in HIV Infection.

HIV infection and antiretroviral therapy (ART) treatment exert diverse effects on adipocytes and stromal-vascular fraction cells, leading to changes in adipose tissue quantity, distribution, and energy storage. A HIV-associated lipodystrophic condition was recognized early in the epidemic, characterized by clinically apparent changes in subcutaneous, visceral, and dorsocervical adipose depots. Underlying these changes is altered adipose tissue morphology and expression of genes central to adipocyte maturation, regulation, metabolism, and cytokine signaling. HIV viral proteins persist in circulation and locally within adipose tissue despite suppression of plasma viremia on ART, and exposure to these proteins impairs preadipocyte maturation and reduces adipocyte expression of peroxisome proliferator-activated receptor gamma (PPAR-γ) and other genes involved in cell regulation. Several early nucleoside reverse transcriptase inhibitor and protease inhibitor antiretroviral drugs demonstrated substantial adipocyte toxicity, including reduced mitochondrial DNA content and respiratory chain enzymes, reduced PPAR-γ and other regulatory gene expression, and increased proinflammatory cytokine production. Newer-generation agents, such as integrase inhibitors, appear to have fewer adverse effects. HIV infection also alters the balance of CD4+ and CD8+ T cells in adipose tissue, with effects on macrophage activation and local inflammation, while the presence of latently infected CD4+ T cells in adipose tissue may constitute a protected viral reservoir. This review provides a synthesis of the literature on how HIV virus, ART treatment, and host characteristics interact to affect adipose tissue distribution, immunology, and contribution to metabolic health, and adipocyte maturation, cellular regulation, and energy storage. © 2017 American Physiological Society. Compr Physiol 7:1339-1357, 2017.

Association of PPARG rs 1801282 C>G polymorphism with risk of colorectal cancer: from a case-control study to a meta-analysis.

The functional single nucleotide polymorphisms in peroxisome proliferator-activated receptor gamma (PPARG) gene were predicted to be correlated with the susceptibility of colorectal cancer (CRC). The aim of the present study was to explore the relationship between PPARG rs1801282 C>G polymorphism and the risk of CRC. First, we conducted a case-control study with 387 CRC cases and 1,536 controls. We used the SNPscan method to determine the genotypes of PPARG rs1801282 C>G polymorphism. We found PPARG rs1801282 C>G polymorphism had a tendency of decreased risk to CRC risk (CG vs. CC: adjusted OR, 0.67, 95% CI = 0.43–1.04 for CG vs. CC, P = 0.073; GG vs. CC: adjusted OR, 0.68; 95% CI, 0.44–1.05; P = 0.078). The stratified analysis revealed PPARG rs1801282 C>G polymorphism also had a tendency of decreased risk to colon cancer (CG vs. CC: adjusted OR = 0.54, 95% CI = 0.27–1.08, P = 0.083). The results of subsequent meta-analysis suggested that PPARG rs1801282 C>G polymorphism might be a protective factor for CRC, especially in Asians, colon cancer and rectum cancer subgroups. In conclusion, our study indicates that PPARG rs1801282 C>G polymorphism might decrease the risk of overall CRC. Larger sample size and well-designed case-control studies are needed to confirm the potential association.

Effects of Dendrobium officinale polysaccharide on adipogenic differentiation of rat bone marrow mesenchymal stem cells

Abstract This study investigated the effect of Dendrobium officinale polysaccharide (DOP) on the adipogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs). DOP was extracted fresh Dendrobium officinale. Rat BMSCs were prepared, and then were treated with 0 (control), 50, 100, 200, 400, 800 μg/mL DOP, respectively. The cell viability was determined by MTT assay. The adipogenic differentiation was quantitatively analyzed by oil red O staining assay. The mRNA expressions of adipogenic differentiation related gene peroxisome proliferator-activated receptor gamma (PPARG), lipoprotein lipase (LPL) and fatty acid binding protein 4 (FABP4) were detected by RT-PCR. Results showed that, DOP with 0-800 μg/mL concentration had no significant toxicity to BMSCs. 200-800 μg/mL DOP could obviously inhibit the adipogenic differentiation of BMSCs. Compared with control group, the expression levels of PPARG, LPL and FABP4 mRNA 200, 400 and 800 μg/mL DOP groups were significantly decreased (P < 0.05 or P < 0.01). DOP can inhibit the adipogenic differentiation of BMSCs, which may be related with its down-regulation of PPARG, LPL and FABP4 expressions in BMSCs.

MRNA expression of nuclear factor of activated T-cells, cytoplasmic 2 (NFATc2) and peroxisome proliferator-activated receptor gamma (PPARG) transcription factors in colorectal carcinoma.

Transcription factors are involved in cell cycle and apoptosis regulation and thus have a key role in the carcinogenesis of different tumors. Nuclear factor of activated T-cells, cytoplasmic 2 (NFATc2) and peroxisome proliferator-activated receptor gamma (PPARG) transcription factors are important in the carcinogenesis of colorectal cancer (CRC). In this study, we examined whether the expression of NFATc2 and PPARG genes is significantly altered during the carcinogenesis of CRC. A total of 47 tumor samples and matched normal tissue margins were collected during surgery from patients with CRC. In addition, three CRC cell lines (HCT119, SW480, and HT29) and healthy cell line were used. After total RNA extraction and cDNA synthesis, mRNA expression levels of NFATc2 and PPARG were examined by real-time polymerase chain reaction. The results showed that NFATc2 is overexpressed in the tumor tissues compared with normal tissue margins (p ≤ 0.05). However, the mRNA expression levels of PPARG were not significantly different between the tumor tissues and tissue margins. Our results indicate that NFATc2 may be used as an early diagnostic or predictive biomarker for CRC as well as a therapeutic target, providing that upcoming studies confirm these results.

The ADAMTS9 gene is associated with cognitive aging in the elderly in a Taiwanese population.

Evidence indicates that the pathophysiologic mechanisms associated with insulin resistance may contribute to cognitive aging and Alzheimer’s diseases. In this study, we hypothesize that single nucleotide polymorphisms (SNPs) within insulin resistance-associated genes, such as the ADAM metallopeptidase with thrombospondin type 1 motif 9 (ADAMTS9), glucokinase regulator (GCKR), and peroxisome proliferator activated receptor gamma (PPARG) genes, may be linked with cognitive aging independently and/or through complex interactions in an older Taiwanese population. A total of 547 Taiwanese subjects aged over 60 years from the Taiwan Biobank were analyzed. Mini-Mental State Examinations (MMSE) were administered to all subjects, and MMSE scores were used to measure cognitive functions. Our data showed that four SNPs (rs73832338, rs9985304, rs4317088, and rs9831846) in the ADAMTS9 gene were significantly associated with cognitive aging among the subjects (P = 1.5 x 10−6 ~ 0.0002). This association remained significant after performing Bonferroni correction. Additionally, we found that interactions between the ADAMTS9 rs9985304 and ADAMTS9 rs76346246 SNPs influenced cognitive aging (P < 0.001). However, variants in the GCKR and PPARG genes had no association with cognitive aging in our study. Our study indicates that the ADAMTS9 gene may contribute to susceptibility to cognitive aging independently as well as through SNP-SNP interactions.

Beta-sitosterol upregulated paraoxonase-1 via peroxisome proliferator-activated receptor-γ in irradiated rats.

This study was designed to evaluate the effect of beta-sitosterol (BS) on the peroxisome proliferator-activated receptor gamma (PPAR-γ) gene expression role in the activity of paraoxonase (PON-1) enzyme in oxidative stress status of irradiated rats. Animals were exposed to whole body γ-radiation single dose 6 Gy and received BS dose (40 mg·(kg body mass)-1·day -1, orally). In liver tissue, gene expression of PPAR-γ ligand was determined. Oxidative stress marker (malondialdehyde, MDA) and antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT), PON-1, and arylesterase (ARE)) were assayed in serum and liver tissue. Also, serum lipid profile (cholesterol, triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)) was measured. In irradiated animals that received BS, expression of PPAR-γ ligand increase significantly associated with increase in PON-1 and ARE enzyme activities. Also, the activities of SOD, CAT enzymes, and HDL-c levels display elevation. By contrast, significant decrease in MDA content, cholesterol, TG, and LDL-c levels were revealed after BS administration. Our findings in this study provide the evidence that BS has radio-protective effect via regulating the gene expression of PPAR-γ, causing an increase in PON-1 and ARE enzyme activities. This action of BS is due to its free radical scavenging properties, antioxidant effect, lowering of cholesterol, and PPAR-γ agonist properties.

Maternal vitamin D deficiency during pregnancy affects expression of adipogenic-regulating genes peroxisome proliferator-activated receptor gamma (PPARγ) and vitamin D receptor (VDR) in lean male mice offspring.

Maternal vitamin D deficiency during pregnancy is a widespread issue that may have long-lasting consequences on offspring adiposity. We sought to determine how maternal vitamin D deficiency during the perinatal period would affect offspring adipose tissue development and gene expression. Female C57BL/6J mice were fed either a vitamin D deficient (VDD) or control diet from 4weeks before pregnancy (periconception) until 7days postparturition. Male offspring were weighed and euthanized at 75days of age (early adult period), at which point serum was collected for biochemical analyses, and perigonadal and subcutaneous white adipose tissue (PGAT and SQAT, respectively) were excised, weighed, then flash-frozen for later histology and analyses of adipogenic gene expression. All adult male offspring were nonobese; there were no significant differences in body weight, adipose pad weight, or adipocyte size. However, VDD-exposed offspring had greater expression of the adipogenic-regulating genes peroxisome proliferator-activated receptor gamma (Pparg) and vitamin D receptor (Vdr). This study suggests that exposure to vitamin D deficiency during the perinatal period can directly affect genes involved in the development of adipose tissue in nonobese offspring. These novel findings invite further investigation into the mechanisms by which maternal vitamin D status during pregnancy affects adipose development and metabolic health of offspring.

C75 Fatty Acid Synthesis (FAS) Inhibitor Has Potent Immunosuppressive Activity

Fatty acid synthesis (FAS) or oxidation (FAO) are important regulatory pathways in immune response. In fact, FAS plays a pivotal role in antigen presentation and T cells activation and FAO leads to fatty acid degradation which has been previously shown to regulate hematopoietic stem cell maintenance. Here we hypothesized that FAS can be a new target to suppress T cell alloimmune responses in solid organ or stem cell transplantations. Therefore, we tested if the FAS inhibitor C75 could suppress T cell alloreactivity without impairing normal hematopoiesis.The immuno-suppressive (IS) effect of moderate FAS inhibition was demonstrated in mixed leukocyte cultures (MLC) where C75 at 10 mkg/ml significantly reduced T cell proliferation and prevented the expansion of CD3+CD25+ and CD3+CD69+ T cells. In T cells stimulated by alloantigen, C75 also induced the downregulation of NF-kB gene expression and the upregulation of peroxisome proliferator-activated receptor gamma (PPARγ) gene involved in ubiquitination and degradation of NF-kB protein.When compared to other standard IS agents, such as anti-thymocyte globulin (ATG), Cyclosporine A, Rapamycin or inhibitor of FAO Etomoxir, C75 showed similar anti-T cell activity.The same dose of C75 (10 mkg/ml) did not cause apoptotic death of human CD34+ cells in vitro, nor affected CD34+ cell clonogenicity in vitro. In fact, C75 increased the number of BFU-E and CFU-GM colonies (P < 0.05). We observed that the expression of de novo DNA methyltrasferases DNMT3A and DNMT3B, which are important regulators of stem cell renewal, was strongly reduced in CD34+ cells co-cultured for 3 days with allogeneic T cells. On the contrary, in the presence of C75 the expression of DNMT3A and DNMT3B was not different from baseline control. To test the in-vivo effect of C75 we utilized a xenograft model of stem cell rejection where 2 x 105 human CD34+ cells and HLA incompatible T lymphocytes were injected in immunodeficient nonobese diabetic/ltsz-scid/scid - IL2 receptor gamma chain knockout (NSG) mice at 1:1 ratio. Four weeks after transplantation, control NSG mice showed complete rejection of huCD45+CD34+ cells and the expansion of T cells in the marrow and spleen. NSG mice treated with intra-peritoneum injections of C75 every 3 days for 2 weeks, instead, showed 10-15% human CD45+ myeloid cells in the marrow and spleen at week 4 after transplant, suggesting at least a partial effect on preventing rejection of incompatible stem cells.We showed here that moderate FAS inhibition may represent a novel immunosuppressive strategy and our findings will prompt preclinical investigations exploiting the effect of FAS inhibitors alone or in combination with standard IS agents in models of allogeneic transplantation or bone marrow failure. DisclosuresNo relevant conflicts of interest to declare.

PPARG gene C161T CT/TT associated with lower blood lipid levels and ischemic stroke from large-artery atherosclerosis in a Han population in Guangdong

Objective: Peroxisome proliferator-activated receptor gamma (PPARG) is a transcription factor involved in atherosclerosis and related diseases. In this study, we aimed to investigate whether PPARG C161T was associated with lipid levels and large-artery atherosclerosis (LAA) ischemic stroke in a Han Chinese population in Guangdong province.Methods: The genotype PPARG C161T in 149 LAA ischemic stroke patients and 125 healthy controls was examined by polymerase chain reaction-restriction fragment length polymorphism (RFLP) assay. Associations with LAA ischemic stroke were analyzed for PPARG C161T genotype, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), and a logistic regression analysis was performed to identify risk factors for LAA ischemic stroke.Results: The frequency of CC was higher than that of CT + TT and was significantly associated with LAA ischemic stroke. In both the LAA and control groups, TC and LDL-C levels were significantly higher in the CC type than the CT + TT, but TG and HDL-C levels were comparable. The only verified independent risk factors for LAA ischemic stroke were ischemic heart disease (OR: 2.784, 95% CI: 1.377–5.632; p = 0.004) and systolic blood pressure (OR: 1.014, 95% CI: 1.001–1.026; p = 0.029); the PPARG C161T allele was not independently associated with an increased risk of LAA ischemic stroke (OR = 0.697, 95% CI: 0.372–1.305; p = 0.260).Conclusion: In this Han population, PPARG C161T CT/TT was associated with LAA ischemic stroke and lower levels of blood TC and LDL-C, but was not an independent risk factor for LAA ischemic stroke.

Influence of hatch time and access to feed on intramuscular adipose tissue deposition in broilers

The effect of hatch time and subsequent access to feed on intramuscular adipose tissue deposition was studied in the pectoralis major muscle of male Ross 308 broiler chickens. Based on their hatch time chicks were classified as early (EH), midterm (MH), or late (LH) hatchers, with an average incubation duration of 497.7 h for EH, 508.8 h for MH, and 514.5 h for LH birds. Chicks were provided access to feed either immediately at hatch, or 24 h after the conclusion of the hatch window. Expression of the adipogenic regulatory genes peroxisome proliferator-activated receptor gamma (PPARγ), and stearoyl-CoA desaturase (SCD), were measured at the time of hatch, and zero, one, 4, 7, 28, and 40 d. Intramuscular adipocyte cell width and visualization of adipose tissue deposition was observed at 28 and 40 d. Expression of PPARγ was increased in the pectoralis major of LH birds at the time of hatch, zero, and one d. The expression of PPARγ at one and 7 d, and SCD at 7 d were increased in all birds that received delayed access to feed. At 28 d, adipocyte cell width was increased in LH birds with delayed access to feed, compared to EH and MH birds with delayed access to feed and LH birds with immediate access to feed. At 40 d, adipocyte cell width was increased in all birds that received delayed access to feed. Also at 40 d, there was a trend (P = 0.078) for more extensive intramuscular adipose tissue deposition in LH than EH birds, and in birds with delayed access to feed (P = 0.075). These data indicate delayed access to feed increases intramuscular adipose tissue deposition in the pectoralis major muscle, and suggest that hatch time influences this regulation.

A novel thermoregulatory role for PDE10A in mouse and human adipocytes.

Phosphodiesterase type 10A (PDE10A) is highly enriched in striatum and is under evaluation as a drug target for several psychiatric/neurodegenerative diseases. Preclinical studies implicate PDE10A in the regulation of energy homeostasis, but the mechanisms remain unclear. By utilizing small‐animal PET/MRI and the novel radioligand [18F]‐AQ28A, we found marked levels of PDE10A in interscapular brown adipose tissue (BAT) of mice. Pharmacological inactivation of PDE10A with the highly selective inhibitor MP‐10 recruited BAT and potentiated thermogenesis in vivo. In diet‐induced obese mice, chronic administration of MP‐10 caused weight loss associated with increased energy expenditure, browning of white adipose tissue, and improved insulin sensitivity. Analysis of human PET data further revealed marked levels of PDE10A in the supraclavicular region where brown/beige adipocytes are clustered in adults. Finally, the inhibition of PDE10A with MP‐10 stimulated thermogenic gene expression in human brown adipocytes and induced browning of human white adipocytes. Collectively, our findings highlight a novel thermoregulatory role for PDE10A in mouse and human adipocytes and promote PDE10A inhibitors as promising candidates for the treatment of obesity and diabetes.

Curcuma longa polyphenols improve insulin-mediated lipid accumulation and attenuate proinflammatory response of 3T3-L1 adipose cells during oxidative stress through regulation of key adipokines and antioxidant enzymes.

Plant polyphenols may exert beneficial action against obesity-related oxidative stress and inflammation which promote insulin resistance. This study evaluated the effect of polyphenols extracted from French Curcuma longa on 3T3-L1 adipose cells exposed to H2 O2 -mediated oxidative stress. We found that Curcuma longa extract exhibited high amounts of curcuminoids identified as curcumin, demethoxycurcumin, and bisdemethoxycurcumin, which exerted free radical-scavenging activities. Curcuma longa polyphenols improved insulin-mediated lipid accumulation and upregulated peroxisome proliferator-activated receptor-gamma gene expression and adiponectin secretion which decreased in H2 O2 -treated cells. Curcuminoids attenuated H2 O2 -enhanced production of pro-inflammatory molecules such as interleukin-6, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and nuclear factor κappa B. Moreover, they reduced intracellular levels of reactive oxygen species elevated by H2 O2 and modulated the expression of genes encoding superoxide dismutase and catalase antioxidant enzymes. Collectively, these findings highlight that Curcuma longa polyphenols protect adipose cells against oxidative stress and may improve obesity-related metabolic disorders. © 2016 BioFactors, 42(4):418-430, 2016.

Genetic characterisation of PPARG, CEBPA and RXRA, and their influence on meat quality traits in cattle

BackgroundPeroxisome proliferator-activated receptor gamma (PPARG), CCAAT/enhancer binding protein alpha (CEBPA) and retinoid X receptor alpha (RXRA) are nuclear transcription factors that play important roles in regulation of adipogenesis and fat deposition. The objectives of this study were to characterise the variability of these three candidate genes in a mixed sample panel composed of several cattle breeds with different meat quality, validate single nucleotide polymorphisms (SNPs) in a local crossbred population (Angus - Hereford - Limousin) and evaluate their effects on meat quality traits (backfat thickness, intramuscular fat content and fatty acid composition), supporting the association tests with bioinformatic predictive studies.ResultsGlobally, nine SNPs were detected in the PPARG and CEBPA genes within our mixed panel, including a novel SNP in the latter. Three of these nine, along with seven other SNPs selected from the Single Nucleotide Polymorphism database (SNPdb), including SNPs in the RXRA gene, were validated in the crossbred population (N = 260). After validation, five of these SNPs were evaluated for genotype effects on fatty acid content and composition. Significant effects were observed on backfat thickness and different fatty acid contents (P < 0.05). Some of these SNPs caused slight differences in mRNA structure stability and/or putative binding sites for proteins.ConclusionsPPARG and CEBPA showed low to moderate variability in our sample panel. Variations in these genes, along with RXRA, may explain part of the genetic variation in fat content and composition. Our results may contribute to knowledge about genetic variation in meat quality traits in cattle and should be evaluated in larger independent populations.Electronic supplementary materialThe online version of this article (doi:10.1186/s40781-016-0095-3) contains supplementary material, which is available to authorized users.