Adipose Tissue mRNA Expression Research Articles

Impact of glucose fluctuation on the paracrine secretome profile of human epicardial adipocyte

Abstract Background Glucose fluctuations (GF) is known to be the significant factor related to poor cardiovascular outcome in the diabetic patients. We investigated the potential impact of GF on paracrine effect of human epicardial adipocyte on cardiomyocyte. Methods Human EAT biopsies obtained during surgery and isolated preadipocyte/adipocytes were used to evaluate the direct impact of GF on the adipocytes. Matured adipocytes were exposed to the media containing normal glucose (100 mg/dl, NG), high glucose (300 mg/dl, HG), or high-low glucose (75-300 mg/dl, GF) for 1 week. Transcriptomic profiling of the cultured matured adipocyte was performed using microarray analysis. The impact of GF on the paracrine effect of adipocyte was evaluated using a co-culture with human iPS-derived atrial cardiomyocytes and the adipocytes. Clinical association study verified the validity of the findings. Results GF for 1 week altered the expression of 595 differentially expressed genes (up-regulated or down-regulated) with an effect size of >50% or `−50% and a significant statistical difference (P < 0.05) in human epicardial adipocytes, while the continuous HG for 1 week altered the expression of only 182 differentially expressed genes. Of the genes affected by GF, top 3 most affected genes included IL1β, IL33, IL8. Regarding the other major pro-inflammatory cytokines, IL1α, CCL2 and IL6 were also significantly increased in the adipocyte treated with GF, however these were not increased in the adipocyte treated with HG. Co-culture of human iPS cell-derived atrial cardiomyocytes and adipocytes treated with NG, HG and GF revealed that GF-treated adipocyte strikingly increased oxidative stress in the cardiomyocyte through the paracrine effect. In the real-world clinical association study, IL1β mRNA expression in human epicardial adipose tissue showed significant positive correlation with the severity of GF during hospitalization and oxidative stress in the left atrial myocardium. Conclusions GF adversely affect the paracrine secretome profile of human epicardial adipocyte. IL1β may be a critical epicardial adipocyte-derived adipokine that is enhanced by GF.

Sex-dependent effects of a high fat diet on metabolic disorders, intestinal barrier function and gut microbiota in mouse

Obesity is often associated with sex-dependent metabolic complications, in which altered intestinal barrier function and gut microbiota contribute. We aimed to characterize in mice the sex-dependent effects of a high fat diet on these parameters. Male and female C57BL/6 mice received a standard (SD) or high fat diet (HFD; 60% kcal from fat) during 14 weeks (W14). Body composition, glucose tolerance, insulin sensitivity, intestinal permeability, colonic expression of 44 genes encoding factors involved in inflammatory response and gut barrier function, cecal microbiota, plasma adipokines and white adipose tissue response have been assessed. Both male and female HFD mice exhibited an increase of body weight and fat mass gain and glucose intolerance compared to SD mice. However, only male HFD mice tended to develop insulin resistance associated to increased Tnfα and Ccl2 mRNA expression in perigonadal adipose tissue. By contrast, only female HFD mice showed significant intestinal hyperpermeability that was associated with more markedly altered colonic inflammatory response. Cecal microbiota richness was markedly reduced in both sexes (Observed species) with sex-dependent modifications at the phyla or family level, e.g. decreased relative abundance of Bacillota and Lachnospiraceae in females, increased of Bacteroidaceae in males. Interestingly, some of these microbiota alterations were correlated with peripheral metabolic and inflammatory markers. In conclusions, male and female mice exhibit different responses to a high fat diet with specific changes of gut microbiota, intestinal barrier function, colonic and white adipose tissue inflammation, metabolic markers and body weight gain. The underlying mechanisms should be deciphered in further investigations.

Https://www.texilajournal.com/public-health/article/2527-guardians-of-liver

Glyphosate is used as an herbicide in agriculture. At sub-agriculture concentrations, glyphosate-based herbicide inhibits cell proliferation. Glyphosate is a chelating agent that interferes with the metabolic activities in plants thereby adversely affecting its metabolism. The study aimed to determine the glyphosate-induced detrimental changes in SREBP-1c and PPAR-γ mRNA expression in adipose tissue of adult male rats. Adult male Wistar albino rats were divided into 4 groups, each consisting of 6 animals. Group I served as normal control rats; Group II-IV consisted of rats exposed to glyphosate at different concentrations (50, 100, and 250 mg/kg body weight respectively) orally for 16 weeks. After 16 weeks of treatment, the animals were sacrificed, and adipose tissue was dissected out for the assessment of SREBP-1c and PPAR-γ mRNA by real-time PCR using gene-specific down-regulated primers. The results with the p<0.05 level were considered to be statistically significant. The results showed a significant dose-dependent increase (P <0.05) in the expression of SREBP-1c in all the glyphosate-exposed rats compared to control rats and PPAR-γ mRNA expression was found to be significantly reduced in a concentration-dependent manner (P<0.05) compared to normal control animals. The current findings for the first time report that glyphosate had detrimental changes in the expression of transcription factors such as SREBP-1c and PPAR-γ mRNA in adipose tissue and thereby glyphosate may lead to the development of type-2 diabetes or insulin resistance.

Role of human Kallistatin in glucose and energy homeostasis in mice

ObjectiveKallistatin (KST), also known as SERPIN A4, is a circulating, broadly acting human plasma protein with pleiotropic properties. Clinical studies in humans revealed reduced KST levels in obesity. The exact role of KST in glucose and energy homeostasis in the setting of insulin resistance and type 2 diabetes is currently unknown. MethodsKallistatin mRNA expression in human subcutaneous white adipose tissue (sWAT) of 47 people with overweight to obesity of the clinical trial “Comparison of Low Fat and Low Carbohydrate Diets With Respect to Weight Loss and Metabolic Effects (B-SMART)” was measured. Moreover, we studied transgenic mice systemically overexpressing human KST (hKST-TG) and wild type littermate control mice (WT) under normal chow (NCD) and high-fat diet (HFD) conditions. ResultsIn sWAT of people with overweight to obesity, KST mRNA increased after diet-induced weight loss. On NCD, we did not observe differences between hKST-TG and WT mice. Under HFD conditions, body weight, body fat and liver fat content did not differ between genotypes. Yet, during intraperitoneal glucose tolerance tests (ipGTT) insulin excursions and HOMA-IR were lower in hKST-TG (4.42 ± 0.87 AU, WT vs. 2.20 ± 0.27 AU, hKST-TG, p < 0.05). Hyperinsulinemic euglycemic clamp studies with tracer-labeled glucose infusion confirmed improved insulin sensitivity by higher glucose infusion rates in hKST-TG mice (31.5 ± 1.78 mg/kg/min, hKST-TG vs. 18.1 ± 1.67 mg/kg/min, WT, p < 0.05). Improved insulin sensitivity was driven by reduced hepatic insulin resistance (clamp hepatic glucose output: 7.7 ± 1.9 mg/kg/min, hKST-TG vs 12.2 ± 0.8 mg/kg/min, WT, p < 0.05), providing evidence for direct insulin sensitizing effects of KST for the first time. Insulin sensitivity was differentially affected in skeletal muscle and adipose tissue. Mechanistically, we observed reduced Wnt signaling in the liver but not in skeletal muscle, which may explain the effect. ConclusionsKST expression increases after weight loss in sWAT from people with obesity. Furthermore, human KST ameliorates diet-induced hepatic insulin resistance in mice, while differentially affecting skeletal muscle and adipose tissue insulin sensitivity. Thus, KST may be an interesting, yet challenging, therapeutic target for patients with obesity and insulin resistance.

Zinc Transporter ZnT1 mRNA Expression Is Negatively Associated with Leptin Serum Concentrations but Is not Associated with Insulin Resistance or Inflammatory Markers in Visceral Adipose Tissue.

The aim of this study was to evaluate the relationship between biomarkers of chronic inflammation, insulin resistance, and zinc transporter ZnT1 expression in human visceral adipose tissue. Visceral adipose tissue obtained from 47 adults undergoing laparoscopic surgery for cholecystectomy was used to analyze ZnT1 mRNA expression by RT-qPCR. ZnT1 mRNA levels were compared between subjects with normal weight, overweight, and obesity. A significantly lower ZnT1 expression was observed in overweight and obesity compared with normal-weight subjects (p = 0.0016). Moreover, subjects with normal weight had significantly higher serum zinc concentration (97.7 ± 13.1mg/L) than subjects with overweight (87.0 ± 12.8mg/L) and obesity (83.1 ± 6.6mg/L) (p = 0.002). Pearson test showed a positive correlation between serum zinc concentrations and ZnT1 mRNA expression in visceral adipose tissue (r = 0.323; p = 0.031) and a negative correlation with body mass index (r = - 0.358; p = 0.013). A linear regression model was used to analyze the associations between ZnT1 mRNA expression and serum zinc levels, insulin resistance (HOMA2-IR), serum adipokines (leptin and adiponectin), and serum inflammation biomarkers (tumor necrosis factor alpha, interleukin-6, and C-reactive protein). Interestingly, leptin concentrations were negatively associated with ZnT1 mRNA expression (p = 0.012); however, no significant associations were found for the rest of the analyzed variables. Future research is needed to analyze the causality of negative association between ZntT1 expression in visceral adipose tissue and leptin.

Molecular Approach to Identify Anti-inflammatory Potential of Stevioside in HFD-induced Type 2 Diabetic Rats: Evidence From in Vivo Study

Stevioside is a natural sweetener derived from the leaves of the Stevia rebaudiana plant. It has gained popularity as a sugar substitute due to its intense sweetness without adding calories or affecting blood sugar levels, making it a suitable option for people with diabetes or those looking to reduce their sugar intake. Studies have shown that stevioside has glucose lowering effects. Previous studies have shown that it has significant role in skeletal muscle but its role on expression of inflammatory signaling molecules in adipose tissue against high diet and sucrose-induced type-2 diabetes in experimental rats is yet to be done. The current research was undertaken to investigate if stevioside could also exert its antidiabetic effects by circumventing adipocyte induced inflammation, a key driving factor for insulin resistance in obese individuals. Effective dose of stevioside (20 mg/kg b.wt) was administered orally for 45 days to high fat diet and sucrose induced type-2 diabetic rats. Interestingly, stevioside treatment restores the elevated serum levels of proinflammatory cytokines including tumor necrosis factor-α (TNF-α) and sterol regulatory element binding protein-1c (SREBP-1c) and enhances Peroxisome Proliferator–activated receptor-γ (PPAR-γ) in adipocytes of diabetic rats. The gene expression of IR, GLUT4 and PPAR-γ mRNA were also significantly activated in stevioside treated groups but reduced IL-1 beta, IlL-6, IKKB, TNF-alpha and NFkB mRNA expression in diabetic adipose tissue. More importantly, stevioside acts very effectively as metformin to circumvent inflammation and insulin resistance in diabetic rats. Our results clearly show that stevioside inhibits obesity induced insulin resistance by ameliorating the inflammatory events and upregulating insulin signalling molecules. Keywords: Stevioside, HFD-T2DM, pro inflammation, insulin signalling; adipose tissue, obesity; signaling pathways; Therapautics.

Abstract 11802: IRF2BP2 Regulates Hormone Sensitive Lipase and Lipolysis in Human Adipocytes and in Mice

Background: IRF2BP2, a transcriptional co-factor, has emerged as a potential regulator of circulating lipid levels based on several coronary artery disease (CAD) genome-wide association studies (GWAS) studies. However, the role of IRF2BP2 in adipocytes, which regulate fat storage, energy expenditure, and fatty acid release, remains unexplored. Our aim is to investigate the role of IRF2BP2 in adipocyte function regulation. Methods: Human adipocyte stem cells (hASC) were differentiated into adipocytes for in vitro studies. We used the CRISPR system and lentiviral expression constructs to knockout (KO) and overexpress (OE) IRF2BP2. Control, IRF2BP2 KO and IRF2BP2 OE adipocytes were assessed by several methods, including RNA-seq, western blot analysis, and functional assessment of lipolysis and glucose uptake. IRF2BP2 chromatin immunoprecipitation (ChIP)-seq was performed in vitro . Adiponectin-Cre mice were crossed with Irf2bp2 flox/flox mice to generate adipocyte-specific KO (AKO) animals. We evaluated the effect of IRF2BP2 KO on adipose morphology and gene profiles. Circulating fatty acids were assessed in control and AKO mice. Results: IRF2BP2 deletion or OE in hASC-differentiated adipocytes did not affect adipocyte differentiation or glucose uptake. However, triglyceride lipolysis was markedly increased in KO cells. Conversely, IRF2BP2 OE suppressed lipolysis. RNA-seq analysis of control vs. IRF2BP2 KO or OE cells identified the enrichment of lipid catabolic pathways. Notably, IRF2BP2 KO upregulated, whereas IRF2BP2 OE downregulated the mRNA and protein levels of LIPE (i.e. hormone sensitive lipase, or HSL). Further, ChIP-seq analysis demonstrates strong binding of IRF2BP2 to a LIPE enhancer, suggesting direct regulation. In mice, Irf2bp2 AKO increased circulating fatty acids, accompanied by a reduction of adipocyte size. LIPE mRNA and protein expression in adipose tissue was also elevated. Finally, Irf2bp2 AKO induces massive adipose tissue inflammation, evidenced by F4/80 staining and chemotaxis gene markers expression. Conclusions: We established IRF2BP2, as a novel transcriptional regulator of adipocyte lipolysis, through the key lipolytic gene LIPE, which may shed light on deciphering the role of IRF2BP2 in CAD.

Paternal developmental thyrotoxicosis disrupts neonatal leptin leading to increased adiposity and altered physiology of the melanocortin system.

The genetic code does not fully explain individual variability and inheritance of susceptibility to endocrine conditions, suggesting the contribution of epigenetic factors acting across generations. We used a mouse model of developmental thyrotoxicosis (Dio3-/- mouse) to analyze endocrine outcomes in the adult offspring of Dio3-/- males using standard methods for body composition, and baseline and fasting hormonal and gene expression determinations in serum and tissues of relevance to the control of energy balance. Compared to controls, adult females with an exposed father (EF females) exhibited higher body weight and fat mass, but not lean mass, a phenotype that was much milder in EF males. After fasting, both EF females and males exhibited a more pronounced decrease in body weight than controls. EF females also showed markedly elevated serum leptin, increased white adipose tissue mRNA expression of leptin and mesoderm-specific transcript but decreased expression of type 2 deiodinase. EF females exhibited decreased serum ghrelin, which showed more pronounced post-fasting changes in EF females than in control females. EF female hypothalami also revealed significant decreases in the expression of pro-opiomelanocortin, agouti-related peptide, neuropeptide Y and melanocortin receptor 4. These markers also showed larger changes in response to fasting in EF females than in control females. Adult EF females showed no abnormalities in serum thyroid hormones, but pituitary expression of thyrotropin-releasing hormone receptor 1 and thyroid gland expression of thyroid-stimulating hormone receptor, thyroid peroxidase and iodotyrosine deiodinase were increased at baseline and showed differential regulation after fasting, with no increase in Trhr1 expression and more pronounced reductions in Tshr, Tpo and Iyd. In EF males, these abnormalities were generally milder. In addition, postnatal day 14 (P14) serum leptin was markedly reduced in EF pups. A paternal excess of thyroid hormone during development modifies the endocrine programming and energy balance in the offspring in a sexually dimorphic manner, with baseline and dynamic range alterations in the leptin-melanocortin system and thyroid gland, and consequences for adiposity phenotypes. We conclude that thyroid hormone overexposure may have important implications for the non-genetic, inherited etiology of endocrine and metabolic pathologies.

Serotonin transporter-deficient mice display enhanced adipose tissue inflammation after chronic high-fat diet feeding.

Serotonin is involved in leukocyte recruitment during inflammation. Deficiency of the serotonin transporter (SERT) is associated with metabolic changes in humans and mice. A possible link and interaction between the inflammatory effects of serotonin and metabolic derangements in SERT-deficient mice has not been investigated so far. SERT-deficient (Sert -/-) and wild type (WT) mice were fed a high-fat diet, starting at 8 weeks of age. Metabolic phenotyping (metabolic caging, glucose and insulin tolerance testing, body and organ weight measurements, qPCR, histology) and assessment of adipose tissue inflammation (flow cytometry, histology, qPCR) were carried out at the end of the 19-week high-fat diet feeding period. In parallel, Sert -/- and WT mice received a control diet and were analyzed either at the time point equivalent to high-fat diet feeding or as early as 8-11 weeks of age for baseline characterization. After 19 weeks of high-fat diet, Sert -/- and WT mice displayed similar whole-body and fat pad weights despite increased relative weight gain due to lower starting body weight in Sert -/-. In obese Sert -/- animals insulin resistance and liver steatosis were enhanced as compared to WT animals. Leukocyte accumulation and mRNA expression of cytokine signaling mediators were increased in epididymal adipose tissue of obese Sert -/- mice. These effects were associated with higher adipose tissue mRNA expression of the chemokine monocyte chemoattractant protein 1 and presence of monocytosis in blood with an increased proportion of pro-inflammatory Ly6C+ monocytes. By contrast, Sert -/- mice fed a control diet did not display adipose tissue inflammation. Our observations suggest that SERT deficiency in mice is associated with inflammatory processes that manifest as increased adipose tissue inflammation upon chronic high-fat diet feeding due to enhanced leukocyte recruitment.

Zinc deficiency and a high-fat diet during growth: Metabolic and adipocyte alterations in rats

Background and aimsTo evaluate the effects of a high-fat diet during post-weaning growth on intermediate metabolism and retroperitoneal adipose tissue, in adult male rats exposed to adequate or deficient zinc intake during prenatal and postnatal life. Methods and resultsFemale Wistar rats were fed low- or control-zinc diets from pregnancy to offspring weaning. Male offspring born from control mothers were fed either control or high-fat, control-zinc diets for 60 days. Male offspring born from zinc deficient mothers were fed either low-zinc or high-fat, low-zinc diets for 60 days. At 74 days of life, oral glucose tolerance test was performed. In 81-day-old offspring, blood pressure, lipid profile, plasmatic lipid peroxidation and serum adiponectin level were determined. In retroperitoneal adipose tissue, we evaluated oxidative stress, morphology and adipocytokines mRNA expression. Low-zinc diet induced adipocytes hypertrophy, increased oxidative stress, and decreased adiponectin mRNA expression in adipose tissue. Low-zinc diet increased systolic blood pressure, triglyceridemia, plasmatic lipid peroxidation and glycemia at 3 h after glucose overload. Animals fed high-fat or high-fat, low-zinc diets showed adipocytes hypertrophy, decreased adiponectin mRNA expression, and increased leptin mRNA expression and oxidative stress in adipose tissue. They also exhibited decreased serum adiponectin levels, increased triglyceridemia, plasmatic lipid peroxidation and area under the oral glucose tolerance curve. High-fat, low-zinc diet induced greater alterations in adipocyte hypertrophy, leptin mRNA expression and glucose tolerance test than high-fat diet. ConclusionZinc deficiency since early stages of intrauterine life could increase susceptibility to metabolic alterations induced by high-fat diets during postnatal life.

Post-Effects of Time-Restricted Feeding against Adipose Tissue Inflammation and Insulin Resistance in Obese Mice.

Time-restricted feeding (TRF) has been shown to improve the disordered metabolic and immunologic functions associated with obesity, however little is known about its post-effects after the cessation of TRF practice. In the current study, we determined how long the effects of TRF persist, and whether the effects are tissue-dependent. There were four groups of mice in this study: overweight and obese mice were randomized into (1) TRF group (TRF for 6 weeks), (2) post-TRF group (TRF for 4 weeks and later ad libitum), (3) continuous ad libitum of high-fat diet (HFD-AL), and (4) the lean control-fed low-fat diet ad libitum. Blood, liver, and adipose tissues were collected to measure the metabolic, inflammatory, and immune cell parameters. The results showed that TRF withdrawal quickly led to increased body weight/adiposity and reversed fasting blood glucose. However, fasting insulin and insulin resistance index HOMA-IR remained lower in the post-TRF than in the HFD-AL group. In addition, TRF-induced reduction in blood monocytes waned in the post-TRF group, but the TRF effects on mRNA levels of proinflammatory immune cells (macrophages Adgre1 and Itgax) and cytokine (Tnf) in adipose tissue remained lower in the post-TRF group than in the HFD-AL group. Furthermore, the TRF group was protected from the down-regulation of Pparg mRNA expression in adipose tissue, which was also observed in the post-TRF group to a lesser extent. The post-TRF animals displayed liver mass similar to those in the TRF group, but the TRF effects on the mRNA of inflammation markers in the liver vanished completely. Together, these results indicate that, although the lasting effects of TRF may differ by tissues and genes, the impact of TRF on adipose tissue inflammation and immune cell infiltration could last a couple of weeks, which may, in part, contribute to the maintenance of insulin sensitivity even after the cessation of TRF.

Unraveling the role of resistin, retinol-binding protein 4 and adiponectin produced by epicardial adipose tissue in cardiac structure and function: evidence of a paracrine effect

PurposeAdipokines produced by adipose tissue have been found to be involved in the pathophysiology of metabolic and cardiovascular diseases. We aimed to investigate the relationships of resistin, retinol-binding protein 4 (RBP4) and adiponectin produced by epicardial adipose tissue with coronary artery disease (CAD) and cardiac structure and function.MethodsForty-one non-diabetic males scheduled for cardiothoracic surgery were examined. Anthropometric measurements, echocardiography, coronary angiography, and blood analysis were performed preoperatively. We measured the serum levels of resistin, RBP4, and adiponectin and their mRNA expression in thoracic subcutaneous adipose tissue and two epicardial adipose tissue samples, one close to left anterior descending artery (LAD) (resistin-LAD, RBP4-LAD, adiponectin-LAD), and another close to the right coronary artery (RCA) (resistin-RCA, RBP4-RCA, adiponectin-RCA).ResultsLeft ventricular (LV) ejection fraction correlated negatively with adiponectin-LAD (rho = − 0.390, p = 0.025). The ratio of early to late diastolic transmitral flow velocity, as an index of LV diastolic function, correlated negatively with resistin-LAD (rho = − 0.529, p = 0.024) and RBP4-LAD (rho = − 0.458, p = 0.049). There was no difference in epicardial adipose tissue mRNA expression of resistin, RBP4, and adiponectin between individuals with CAD and those without CAD. When we compared the individuals with CAD in the LAD with those without CAD in the LAD, there was no difference in resistin-LAD, RBP4-LAD, and adiponectin-LAD. There was no difference in resistin-RCA, RBP4-RCA, and adiponectin-RCA between the individuals with CAD in the RCA and those without CAD in the RCA.ConclusionElevation of epicardial adipose tissue mRNA expression of adiponectin was associated with LV systolic dysfunction, while that of both resistin and RBP4 was linked to LV diastolic dysfunction.

Berberine Ameliorates Obesity by Inducing GDF15 Secretion by Brown Adipocytes.

Berberine (BBR), which is a compound derived from the Chinese medicinal plant Coptis chinensis, promotes weight loss, but the molecular mechanisms are not well understood. Here, we show that BBR increases the serum level of growth differentiation factor 15 (GDF15), which is a stress response cytokine that can reduce food intake and lower body weight in diet-induced obese (DIO) mice. The body weight and food intake of DIO mice were decreased after BBR treatment, and the weight change was negatively correlated with the serum GDF15 level. Further studies show that BBR induced GDF15 mRNA expression and secretion in the brown adipose tissue (BAT) of DIO mice and primary mouse brown adipocytes. In addition, we found that BBR upregulates GDF15 mRNA expression and secretion by activating the integrated stress response (ISR) in primary mouse brown adipocytes. Overall, our findings show that BBR lowers body weight by inducing GDF15 secretion via the activation of the ISR in BAT.

Effects of a Calorie-Restricted Cafeteria Diet and Oleuropein Supplementation on Adiposity and mRNA Expression of Energy Balance Related Genes in Obese Male Rats.

Supplementation with natural bioactive compounds has been proposed to be a complementary tool to the calorie-restricted diets and physical exercise programs used to tackle human overweight, obesity and Metabolic syndrome. Herein, we evaluated the effects of 14 weeks of calorie-restricted cafeteria diet either alone or combined with oral administration of the polyphenol oleuropein in obese adult male rats, compared with a control group fed standard chow and a group fed cafeteria diet. Animals were sacrificed at the age of 26 weeks and several tissues of interest were removed. The results showed that both dietary interventions reduced the adiposity index (p < 0.05 and p < 0.01, respectively), and specifically the abdominal fat depots (mesenteric: p < 0.01 and p < 0.01, respectively; and epididymal: both diets p < 0.001) and restored the decreased soleus skeletal muscle mass. Both interventions decreased leptin mRNA expression in mesenteric white adipose tissue (p < 0.05) and normalized hypothalamic Agrp mRNA expression compared to cafeteria-fed obese rats (p < 0.05). However, only the calorie-restricted cafeteria diet supplemented with oleuropein induced additional lower retroperitoneal adipose accretion (p < 0.05) and increased hypothalamic leptin receptor mRNA levels (p < 0.05). Experiments with female animals, at different doses and longer intervention periods, are needed to better determine the potential benefits of this dietary treatment.

Omentin-1 Levels and Outcomes in Incident Peritoneal Dialysis Patients

Omentin-1 is an adipokine with anti-inflammatory and cardioprotective properties. The objective of this study was to determine the prognostic role of plasma omentin-1 levels in incident peritoneal dialysis (PD) patients. Retrospective analysis of prospective cohort. 152 incident PD patients. Plasma omentin-1 level, adipose tissue omentin-1 messenger RNA (mRNA) expression. Patient survival, technique survival, hospital admission, and duration of stay. Time-to-event survival analyses; linear regression for hospitalization. The mean age was 58.4±11.7 years; 102 were men, and 92 had diabetes. There was no significant correlation between plasma omentin-1 level and its adipose tissue mRNA expression. A higher plasma omentin-1 level quartile was not associated with patient survival (P=0.92) or technique survival (P=0.83) but had a modest correlation with a lower number of hospital admissions (P=0.07) and shorter duration of hospital stay (P=0.04). In adjusted models using multivariable linear regression, a higher plasma omentin-1 level quartile remained significantly associated with fewer hospital admissions (β, -0.13; 95% CI, -0.26 to -0.002; P=0.05) and shorter hospitalization duration (β, -0.20; 95% CI, -0.38 to -0.02; P=0.03). Observational study with baseline measures only. Plasma omentin-1 level was not associated with patient survival, technique survival, or peritonitis, but higher plasma omentin-1 levels were associated with fewer hospital admissions and shorter duration of hospitalization among incident PD patients.

γ-Linolenic Acid-Rich Oil- and Fish Oil-Induced Alterations of Hepatic Lipogenesis, Fatty Acid Oxidation, and Adipose Tissue mRNA Expression in Obese KK-&lt;i&gt;A&lt;/i&gt; &lt;sup&gt; &lt;i&gt;y&lt;/i&gt; &lt;/sup&gt; Mice

The physiological activity of γ-linolenic acid (GLA)-rich evening primrose oil and eicosapentaenoic and doxosahexaenoic acids-rich fish oil, which affect hepatic fatty acid oxidation and synthesis, and adipose tissue mRNA expression were compared in diabetic obese KK-A y mice. The mice were fed diets containing 100 g/kg of either palm oil (saturated fat), GLA oil, or fish oil for 21 days. These oils, compared with palm oil, greatly increased the activity and mRNA levels of hepatic fatty acid oxidation enzymes. These oils also increased the carnitine concentrations and mRNA levels of carnitine transporter (solute carrier family 22, member 5) in the liver. In general, these effects were comparable between GLA and fish oils. In contrast, GLA and fish oils, compared with palm oil, reduced the activity and mRNA levels of the proteins related to hepatic lipogenesis, except for those of malic enzyme. The reducing effect was stronger for fish oil than for GLA oil. These changes were accompanied by reductions in the triacylglycerol levels in the serum and liver. The reduction in the liver was stronger for fish oil than for GLA oil. These oils also reduced epididymal adipose tissue weight accompanied by a reduction in the mRNA levels of several proteins that regulate adipocyte functions; these effects were stronger for fish oil than for GLA oil. These oils were also effective in reducing serum glucose levels. Therefore, both fish oil and GLA-rich oil were effective at ameliorating metabolic disorders related to obesity and diabetes mellitus.

Dietary Sinapic Acid Alleviates Adiposity and Inflammation in Diet-Induced Obese Mice.

Sinapic acid (SA), a hydroxycinnamic acid, is known to confer protection against oxidative stress, inflammation, diabetes, and liver disease. However, the effectiveness of SA in improving obesity remains obscure. Therefore, this study evaluated anti-obesity efficacy of SA and to elucidate its mechanism of action. Male mice were maintained for 16 weeks on high-fat diet (HFD) alone or with SA (0.004%, w/w) and bodyweight, fat mass, adipocyte size, food intake, and biochemical and molecular markers were evaluated. SA-supplemented mice demonstrated markedly decreased fat mass and adipocyte size compared to unsupplemented group, without any changes in bodyweight and food intake between the two groups. Plasma adipocytokines levels including leptin, resistin, monocyte chemoattractant protein (MCP)-1 and interleukin-6 were also markedly reduced by SA supplementation. SA tended to lower plasma insulin level and improved homeostatic index of insulin resistance and intraperitoneal glucose tolerance test in HFD-induced obese mice. The anti-adiposity effect of SA was maybe owing to down-regulation of the mRNA expression of lipogenic genes, including acetyl coenzyme A (CoA) carboxylase, fatty acid synthesis, stearoyl-CoA desaturase 1, and phosphatidate phosphatase, and peroxisome proliferator-activated receptor γ, a transcription factor responsible for governing lipid metabolism, in adipose tissues. SA significantly down-regulated pro-inflammatory nuclear factor kappa B, MCP-1, tumor necrosis factor-α, and Toll-like receptor 4 mRNA expression in adipose tissue. Thus, SA could be beneficial for the development of functional foods or herbal medications to combat obesity.

Circulating and Adipose Tissue Adiponectin Level and Outcomes in Incident Peritoneal Dialysis Patients

Cardiovascular disease is the major cause of mortality and morbidity in peritoneal dialysis (PD) patients. Adiponectin, a key adipokine, is related to obesity and insulin resistance. We determined the clinical and prognostic value of plasma adiponectin level and its adipose tissue messenger RNA (mRNA) expression in new PD patients. Retrospective analysis of a prospective observational study. 152 new PD patients from a single center; 6 adults undergoing abdominal surgeries without kidney disease served as controls. Plasma adiponectin level and its adipose tissue mRNA expression. Body build and composition, patient and technique survival. Adiponectin level and mRNA expression were grouped in quartiles for correlation analysis for body build and Cox regression for survival analysis. The median plasma adiponectin level was 31.98μg/mL (IQR, 16.81-49.49μg/mL), and adiponectin mRNA expression in adipose tissue was 1.65 times higher than in controls (IQR, 0.98-2.63). There was a modest but statistically significant correlation between plasma adiponectin and its adipose tissue mRNA expression (r=0.40, P<0.001). Plasma adiponectin level inversely correlated with body mass index, waist-hip ratio, mid-arm circumference, adipose tissue mass, plasma triglyceride (r=-0.39, -0.38, -0.41, -0.38, and -0.30, respectively; P<0.001 for all), as well as serum insulin level (r=-0.24, P=0.005). Similar correlations were present but less marked with adipose tissue adiponectin mRNA level. Neither plasma adiponectin level nor adipose tissue adiponectin mRNA level predicted patient or technique survival. Observational study, single center, single baseline measurement. Plasma adiponectin level correlated with the degree of adiposity in new PD patients. However, neither plasma adiponectin level nor its adipose tissue mRNA expression was an independent prognostic indicator in kidney failure patients newly started on PD.

Associations of Betatrophin/ANGPTL8 with Septic Dyslipidemia in Human Peritonitis: An Explorative Analysis.

Sepsis is defined by life-threatening organ dysfunction mediated by the host's response to infection. This can result in septic dyslipidemia, which is involved in the neutralization of pathogen-related lipids. Knowledge of the regulatory mechanisms of septic dyslipidemia is incomplete. The cytokine betatrophin/Angiopoietin-like protein 8 (ANGPTL8) plays a role in the regulation of triacylglyceride metabolism, though its function in septic dyslipidemia remains unknown. Sixty-six patients were enrolled in a cross-sectional study. Circulating concentrations and adipose tissue (AT) mRNA expression of betatrophin/ANGPTL8 were studied in patients suffering from peritoneal sepsis. Insulin-resistant individuals and subjects without metabolic derangement/systemic inflammation were enrolled as controls. All underwent open abdominal surgery. Circulating betatrophin/ANGPTL8 was analyzed by an enzyme-linked immunosorbent assay and AT mRNA expression levels were assessed by real-time PCR. Standard laboratory analyses including lipid electrophoresis were evaluated. Sepsis patients showed pronounced septic dyslipidemia (p &lt; 0.05 for all major lipid classes). Despite comparable betatrophin/ANGPTL8 mRNA expression in AT (p = 0.24), we found significantly increased circulating betatrophin/ANGPTL8 with septic dyslipidemia (p = 0.009). Expression levels of betatrophin/ANGPTL8 in AT correlated with circulating concentrations in both control groups (r = 0.61; p = 0.008 and r = 0.43; p = 0.034), while this association was undetectable in sepsis. After stratification, betatrophin/ANGPTL8 remained associated with hypertriacylglyceridemia (p &lt; 0.05).

Effect of dietary supplementation withTenebrio molitor wholemeal and fermented flour modulating adipose lipogenesis gene expression in obese mice

The use of insects recently emerged as an alternative source of high-quality animal protein for both animal and human food supplementation use with lower environmental impact. Recent evidence indicates that an insect-based diet provides an improved animal production mass gain and showed benefits for human health. The present study evaluated the dietary supplementation effect of theTenebrio molitor fermented and wholemeal flour on the metabolism of diet-induced obese mice. Male Swiss mice were divided into 4 groups treated for 4 weeks as follows: standard diet, high-fat diet, high-fat diet + wholemeal flour and high-fat diet + fermented flour. The 15% wholemeal or fermented flour were added to the diet. Several parameters such as food/energy intake, body weight, adipose tissue weight, biochemical levels, adipose tissue histology and mRNA expression were evaluated. The main results showed that the inclusion of wholemeal and fermentedT. molitor flour induced body weight loss, adiposity reduction and specific changes in biochemical and histological parameters. In addition, was observed significant changes in lipogenic gene expression. The insect flour negatively modulated the expression of the SREBP1α, CEBP1α, FAS, ACC gene and positively modulated PGC1α. In conclusion, the main findings showed theT. molitor flour potential use to improve dyslipidaemia and adiposity with beneficial effects on metabolic diseases.