Globin Digest Improves Visceral Adiposity Through UCP1 Upregulation in Diet-Induced Obese Zebrafish and Mice.
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SUBMITTER: Zang L
PROVIDER: S-EPMC8502801 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Abstract Objectives The Visceral Adiposity Index (VAI) was developed to estimate adipose tissue dysfunction as well as visceral fat distribution. In an ancillary analysis of the CROSSROADS Study (clinicaltrials.gov #NCT00955903), this study investigated the effects of exercise with and without intentional energy restriction on VAI changes among older adults with obesity. Methods Participants (n = 163, 37.4% male, 70.3 ± 4.7 years) were randomized to the following groups: exercise only, exercise + nutrient-dense weight maintenance diet, and exercise + nutrient-dense energy restriction of 500 kcal/d. Visceral adiposity determined by magnetic resonance imaging (MRI) and dual-energy X-ray absorptiometry (DXA), anthropometrics, and cardiometabolic biomarkers were assessed at baseline and 12 months. Waist circumference, body mass index, triglycerides, and high-density lipoprotein (HDL) cholesterol were used to compute VAI at both time points. Data were analyzed utilizing Spearman's correlations and general linear models to determine differences among groups following adjustment for covariates. Results Among all participants, significant correlations were observed between VAI and glucose, insulin, tumor necrosis factor-alpha (TNF-α), and the adiponectin: leptin ratio at baseline (r = 0.343, P < 0.001; r = 0.363, P < 0.001; r = 0.200, P = 0.011; r = −0.246, P = 0.002, respectively). DXA and MRI measures of visceral adiposity were not significantly correlated with VAI. Upon completion of the 12-month study period, there were significant differences in VAI among groups [F (2,137) = 5.957, P = 0.003)]. Post hoc analysis revealed that VAI was significantly lower in the exercise + nutrient-dense energy restriction group compared to the exercise only group (P = 0.002). Conclusions Results suggest that VAI may be an adequate measure of adipose tissue dysfunction, yet its ability to estimate levels of visceral adiposity warrants further investigation to determine clinical utility. Nonetheless, results suggest that an exercise + nutrient-dense energy restriction intervention may reduce VAI among older adults with obesity. Funding Sources NIH.
| S-EPMC8180756 | biostudies-literature
Project description:Smallanthus sonchifolius (yacon), a native plant of South America, was observed to improve lipid profile in rodents and humans. This study aimed to investigate the antiobesity properties of yacon roots in a high-fat-diet (HFD) model and the underlying mechanisms. A total of 30 Wistar male rats were divided into five groups (n=6): the standard chow diet (SD) group was fed a SD; the HFD group was fed a HFD; and the HFD Y340 and HFD Y680 groups were fed a HFD plus yacon flour (340 and 680 mg FOS/kg b. w./day, respectively). HFD Y340 and HFD Y680 rats exhibited marked attenuation of weight gain, a decrease in visceral fat pad weight, a restoration of the serum lipid profile and atherogenic index in a dose-dependent manner, being the higher dose more effective (p < 0.05). In addition, we found that HFD Y680 rats showed lower glucose and insulin levels, improved glucose tolerance, and insulin sensitivity (p < 0.5). A downregulation of several adipocyte specific-transcription factors, including peroxisome proliferator-activated receptor gamma2 (PPAR-γ2), CCAAT/enhancer binding protein a (C/EBP-a) and activating protein (aP2) mRNA levels, was determined in the visceral adipose tissue of HFD Y680 rats (p < 0.05). An improvement of adipokine profile in HFD Y680 rats and decreased serum proinflammatory cytokine levels (p < 0.05) were determined by ELISA. Decreased macrophage infiltration and F4/80 and MCP-1 expression in the visceral adipose tissue of HFD Y680 rats (p < 0.5), together with a higher pAkt/Akt expression (p < 0.05) were also observed by immunofluorescence and immunoblotting. A significant increase in glucagon (Gcg) and PYY mRNA levels in distal ileum of HFD Y680 rats (p < 0.05) were also detected. In the second approach, we determined that yacon supplementation potentiates the effects of the HFD reversion to a standard diet. In conclusion, yacon showed antiobesity properties by inhibiting adipogenesis and improving the visceral adipose tissue function.
| S-EPMC6230400 | biostudies-literature
Project description:Obesity, and visceral adiposity in particular, increases the risk of common metabolic diseases, including type 2 diabetes, cardiovascular disease, and several forms of cancer. However, the molecular mechanisms responsible for regional fat storage remain poorly characterized, preventing therapeutic innovation. We here applied a systematic genome-wide screen and translational approach, and discovered a novel role for the adipocyte-expressed neutral amino acid transporter SLC7A10/ASC-1 in the regulation of visceral adiposity. Among 65 genes showing both adipose depot-dependent and fat loss-dependent expression, 27 genes further showed significant correlations with waist-to-hip (WHR) ratio adjusted for BMI. Among these ASC-1 was expressed at the highest level in isolated visceral adipocytes. Further, we found decreased ASC-1 mRNA in visceral, and not subcutaneous adipose tissue, in carriers of the KLF14 type 2 diabetes risk allele compared to the protective allele. By profiling amino acid fluxes during adipocyte differentiation in vitro, we found that ASC-1 inhibition by a selective inhibitor decreased adipocyte uptake particularly of serine in mature adipocytes. Interestingly, radiometric amino acid uptake assays showed ASC-1 dependent uptake of the serine D-enantiomere. Using primary human and murine adipocyte models, we uncovered marked effects of inhibiting ASC-1 on mitochondrial respiratory capacity (within hours) and lipid accumulation (within days). Finally, Asc-1 knockout (KO) zebrafish had increased body weight and adipocyte enlargement upon eight-week overfeeding compared to wild-type (WT) fish. RNA sequencing data from zebrafish adipose tissue showed up-regulation of genes involved in fatty acid and lipid metabolism in the ASC-1 KOs, consistent with the increased lipid accumulation in the inhibitor-treated cell models. Additionally, duox, an enzyme involved in ROS generation, showed higher expression in the KOs compared to the WTs. Importantly, we confirmed increased reactive oxygen species (ROS) generation (within minutes and within hours) when inhibiting ASC-1 in our in vitro cell models. Our study points to increased ROS generation and reduced mitochondrial respiratory capacity as central early mechanisms in development of visceral adiposity, and a role for adipocyte D-serine transport via ASC-1 in these processes. Enhancing ASC-1 expression and/or activity in adipocytes, likely through primary effects on one-carbon metabolism and redox balance, is a promising therapeutic strategy for reducing visceral adiposity and related diseases.
2021-01-30 | GSE134733 | GEO
Project description:Objectives. The present study aimed at determining cut-off points of visceral fat to predict NAFLD and analyzed metabolic disorders of obese adolescents. Methods. Cross-sectional study involved 165 obese adolescents ranged in age from 15 to 19 years. Glycemia, hepatic transaminases, lipid profile, and insulin resistance were analyzed. Visceral and subcutaneous fat were measured by ultrasound and body composition by plesthysmography. Results. The NAFLD adolescents had significantly higher values for body mass, BMI-for-age, BMI, total fat, waist circumference, and visceral fat when compared with non-NAFLD obese adolescents in both genders. Moreover, there were significant positive correlations between visceral fat with the variables BMI-for-age (r = 0.325,), TG (r = 0.277), AST (r = 0.509), ALT (r = 0.519), WC (r = 0.390), and visceral/subcutaneous ratio (r = 0.790) for NAFLD group. Total fat, triglycerides, and visceral fat were the independent predictors to NAFLD. Analysis of the ROC curves revealed cut-off points of visceral fat of 4.47?cm for girls and 4.21?cm for boys. Conclusions. The results may suggest that abdominal ultrasonography procedure may be a safe alternative method of assessing visceral adiposity aiming to be considered to the development of preventive and treatment strategies in obese individuals. This clinial trial is registered with ClinicalTrial.gov (NCT01358773).
| S-EPMC3872012 | biostudies-literature
Project description:BackgroundThe chemokine receptor CCR7, expressed on various immune cells, is associated with cell migration and lympho-node homing. Mice lacking Ccr7 are protected from diet-induced obesity and subsequent insulin resistance. We evaluated the mechanism underlying these protective effects from the standpoint of energy expenditure.MethodsWild-type and Ccr7 null mice were fed a high-fat diet, and the regulation of energy metabolism and energy metabolism-related molecules, e.g., Ucp1, Cidea, and Pgc1α, were evaluated.ResultsFood intake did not differ between groups. O2 consumption and CO2 production were higher in Ccr7 null mice than in wild-type mice, despite a similar respiratory quotient and glucose and lipid utilization, suggesting that energy expenditure increased in Ccr7 null mice via enhanced metabolism. In white adipose tissues of Ccr7 null mice, Prdm16, Cd137, Tmem26, Th, and Tbx1 expression increased. Similarly, in brown adipose tissues of Ccr7 null mice, Dio2, Pgc1α, Cidea, Sirt1, and Adiponectin expression increased. In both white and brown adipose tissues, Ucp1 gene and protein expression levels were higher in null mice than in wild-type mice.ConclusionsIn Ccr7 null mice, browning of white adipocytes as well as the activation of brown adipocytes cause enhanced energy metabolism, resulting in protection against diet-induced obesity.
| S-EPMC6610939 | biostudies-literature
Project description:The phytochemical oxyresveratrol has been shown to exert diverse biological activities including prevention of obesity. However, the exact reason underlying the anti-obese effects of oxyresveratrol is not fully understood. Here, we investigated the effects and mechanism of oxyresveratrol in adipocytes and high-fat diet (HFD)-fed obese mice. Oxyresveratrol suppressed lipid accumulation and expression of adipocyte markers during the adipocyte differentiation of 3T3-L1 and C3H10T1/2 cells. Administration of oxyresveratrol in HFD-fed obese mice prevented body-weight gains, lowered adipose tissue weights, improved lipid profiles, and increased glucose tolerance. The anti-obese effects were linked to increases in energy expenditure and higher rectal temperatures without affecting food intake, fecal lipid content, and physical activity. The increased energy expenditure by oxyresveratrol was concordant with the induction of thermogenic genes including Ucp1, and the reduction of white adipocyte selective genes in adipose tissue. Furthermore, Foxo3a was identified as an oxyresveratrol-induced gene and it mimicked the effects of oxyresveratrol for induction of thermogenic genes and suppression of white adipocyte selective genes, suggesting the role of Foxo3a in oxyresveratrol-mediated anti-obese effects. Taken together, these data show that oxyresveratrol increases energy expenditure through the induction of thermogenic genes in adipose tissue and further implicates oxyresveratrol as an ingredient and Foxo3a as a molecular target for the development of functional foods in obesity and metabolic diseases.
| S-EPMC6337118 | biostudies-literature
Project description:Artificial proteins representing the consensus of a set of homologous sequences have attracted attention for their increased thermodynamic stability and conserved activity. Here, we applied the consensus approach to a b-type heme-binding protein to inspect the contribution of a dissociable cofactor to enhanced stability and the chemical consequences of creating a generic heme environment. We targeted the group 1 truncated hemoglobin (TrHb1) subfamily of proteins for their small size (∼120 residues) and ease of characterization. The primary structure, derived from a curated set of ∼300 representative sequences, yielded a highly soluble consensus globin (cGlbN) enriched in acidic residues. Optical and NMR spectroscopies revealed high-affinity heme binding in the expected site and in two orientations. At neutral pH, proximal and distal iron coordination was achieved with a pair of histidine residues, as observed in some natural TrHb1s, and with labile ligation on the distal side. As opposed to studied TrHb1s, which undergo additional folding upon heme binding, cGlbN displayed the same extent of secondary structure whether the heme was associated with the protein or not. Denaturation required guanidine hydrochloride and showed that apo- and holoprotein unfolded in two transitions-the first (occurring with a midpoint of ∼2 M) was shifted to higher denaturant concentration in the holoprotein (∼3.7 M) and reflected stabilization due to heme binding, while the second transition (∼6.2 M) was common to both forms. Thus, the consensus sequence stabilized the protein but exposed the existence of two separately cooperative subdomains within the globin architecture, masked as one single domain in TrHb1s with typical stabilities. The results suggested ways in which specific chemical or thermodynamic features may be controlled in artificial heme proteins.
| S-EPMC10432219 | biostudies-literature
Project description:Objective/backgroundWhile obesity is a known risk factor for sleep disordered breathing (SDB), a large proportion of children with SDB are not overweight as per body mass index percentile (BMI%) criteria. This study aimed to examine whether premorbid or concurrent adiposity phenotypes and inflammation are associated with SDB in normal weight youth.Patients/methodsA total of 242 persistently non-overweight (BMI%<85) subjects from the Penn State Child Cohort (PSCC, N = 421, 5-12 y at baseline and 12-23 y at follow-up), were studied. The apnea/hypopnea index (AHI) was ascertained via polysomnography (PSG) at both time points. At follow-up, a dual-energy X-ray absorptiometry (DXA) scan assessed android and gynoid distribution and subcutaneous (SAT) and visceral (VAT) adiposity composition, while a fasting blood draw was assayed for C-reactive protein (CRP) and interleukin-6 (IL-6) levels. Multivariable linear regression models with AHI at follow-up as primary outcome were adjusted for sex, race, adenotonsillectomy, age and AHI at baseline.Results and conclusionsIncreased waist circumference (β = 0.227, p = 0.001) at baseline, but not BMI%, neck or hip circumference, was significantly associated with a higher AHI at follow-up. VAT (β = 0.309, p < 0.001), IL-6 (β = 0.243, p < 0.001), SAT (β = 0.235, p = 0.013), CRP (β = 0.221, p = 0.001), and an android distribution (β = 0.196, p = 0.003) at follow-up were significantly associated with a higher AHI at follow-up. Childhood central adiposity predicts SDB in adolescence, even in individuals who have never been overweight since childhood as per BMI criteria. Visceral adiposity and inflammation are concurrent to adolescent SDB, which supports the clinical utility of these biomarkers in predicting its associated cardiometabolic risk.
| S-EPMC7200279 | biostudies-literature
Project description:Maternal obesity is linked with increased adverse pregnancy outcomes for both mother and child. The metabolic impact of excessive fat within the context of pregnancy is not fully understood. We used a mouse model of high fat (HF) feeding to induce maternal obesity to identify adipose tissue-mediated mechanisms driving metabolic dysfunction in pregnant and non-pregnant obese mice. As expected, chronic HF-feeding for 12 weeks preceding pregnancy increased peripheral (subcutaneous) and visceral (mesenteric) fat mass. However, unexpectedly at late gestation (E18.5) HF-fed mice exhibited a remarkable normalization of visceral but not peripheral adiposity, with a 53% reduction in non-pregnant visceral fat mass expressed as a proportion of body weight (P<0.001). In contrast, in control animals, pregnancy had no effect on visceral fat mass proportion. Obesity exaggerated glucose intolerance at mid-pregnancy (E14.5). However by E18.5, there were no differences, in glucose tolerance between obese and control mice. Transcriptomic analysis of visceral fat from HF-fed dams at E18.5 revealed reduced expression of genes involved in de novo lipogenesis (diacylglycerol O-acyltransferase 2--Dgat2) and inflammation (chemokine C-C motif ligand 20--Ccl2) and upregulation of estrogen receptor α (ERα) compared to HF non pregnant. Attenuation of adipose inflammation was functionally confirmed by a 45% reduction of CD11b+CD11c+ adipose tissue macrophages (expressed as a proportion of all stromal vascular fraction cells) in HF pregnant compared to HF non pregnant animals (P<0.001). An ERα selective agonist suppressed both de novo lipogenesis and expression of lipogenic genes in adipocytes in vitro. These data show that, in a HF model of maternal obesity, late gestation is associated with amelioration of visceral fat hypertrophy, inflammation and glucose intolerance, and suggest that these effects are mediated in part by elevated visceral adipocyte ERα signaling.
| S-EPMC3986097 | biostudies-literature
Project description:Sesamol found in sesame oil has been shown to ameliorate obesity by regulating lipid metabolism. However, its effects on energy expenditure and the underlying molecular mechanism have not been clearly elucidated. In this study, we show that sesamol increased the uncoupling protein 1 (Ucp1) expression in adipocytes. The administration of sesamol in high-fat diet (HFD)-fed mice prevented weight gain and improved metabolic derangements. The three-week sesamol treatment of HFD-fed mice, when the body weights were not different between the sesamol and control groups, increased energy expenditure, suggesting that an induced energy expenditure is a primary contributing factor for sesamol's anti-obese effects. Consistently, sesamol induced the expression of energy-dissipating thermogenic genes, including Ucp1, in white adipose tissues. The microarray analysis showed that sesamol dramatically increased the Nrf2 target genes such as Hmox1 and Atf3 in adipocytes. Moreover, 76% (60/79 genes) of the sesamol-induced genes were also regulated by tert-butylhydroquinone (tBHQ), a known Nrf2 activator. We further verified that sesamol directly activated the Nrf2-mediated transcription. In addition, the Hmox1 and Ucp1 induction by sesamol was compromised in Nrf2-deleted cells, indicating the necessity of Nrf2 in the sesamol-mediated Ucp1 induction. Together, these findings demonstrate the effects of sesamol in inducing Ucp1 and in increasing energy expenditure, further highlighting the use of the Nrf2 activation in stimulating thermogenic adipocytes and in increasing energy expenditure in obesity and its related metabolic diseases.
| S-EPMC7284577 | biostudies-literature