Association Between Adipose Tissue Characteristics and Metabolic Flexibility in Humans: A Systematic Review.
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ABSTRACT:
SUBMITTER: Glaves A
PROVIDER: S-EPMC8678067 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Metabolic flexibility is the capacity for skeletal muscle to shift reliance between lipids and glucose during fasting or in response to insulin. We hypothesized that body fat, adipose tissue characteristics, e.g. larger adipocytes, presence of inflammatory gene markers and impaired suppression of non-esterified fatty acids (NEFAs) during insulin infusion might be related to metabolic flexibility. We measured changes in respiratory quotient (DeltaRQ) before and during euglycemic-hyperinsulinemic clamp in healthy young males. Body fat by DXA, laboratory measurements, abdominal subcutaneous adipose tissue biopsies and fat cell size (FCS) were obtained after an overnight fast. Gene expression for 17 adipose tissue genes related to lipid synthesis, uptake, oxidation and storage, lipolysis and inflammation were measured. Reduced metabolic flexibility was associated with higher body fat, larger FCS and impaired insulin suppression of NEFAs. Metabolic flexibility was associated with higher serum adiponectin levels. Lower adipose tissue gene expression for inflammation markers was associated with greater NEFA suppression by insulin and metabolic flexibility. Combined, these results indicate that body fat, larger adipocytes, failure of insulin to suppress NEFAs, decreased adiponectin levels and inflammation markers in adipose tissue are associated with decreased insulin-stimulated glucose uptake and oxidation, which is an important component of reduced metabolic flexibility.
| S-EPMC2749984 | biostudies-literature
Project description:Epicardial adipose tissue (EAT) is hypothesized to alter atherosclerotic plaque composition, with potential development of high-risk plaque (HRP). EAT can be measured by volumetric assessment (EAT-v) or linear thickness (EAT-t). We performed a systematic review and random-effects meta-analysis to assess the association of EAT with HRP and whether this association is dependent on the measurement method used. Electronic databases were systematically searched up to October 2016. Studies reporting HRP by computed tomography or intracoronary imaging and studies measuring EAT-v or EAT-t were included. Odds ratios were extracted from multivariable models reporting the association of EAT with HRP and described as pooled estimates with 95% confidence intervals (CIs). Analysis was stratified by EAT measurement method. Nine studies (n=3772 patients) were included with 7 measuring EAT-v and 2 measuring EAT-t. Increasing EAT was significantly associated with the presence of HRP (odds ratio: 1.26 [95% CI, 1.11-1.43]; P<0.001). Patients with HRP had higher EAT-v than those without (weighted mean difference: 28.3 mL [95% CI, 18.8-37.8 mL]; P<0.001). EAT-v was associated with HRP (odds ratio: 1.19 [95% CI, 1.06-1.33]; P<0.001); however, EAT-t was not (odds ratio: 3.09 [95% CI, 0.56-17]; P=0.2). Estimates remained significant when adjusted for small-study effect bias (odds ratio: 1.13 [95% CI, 1.03-1.28]; P=0.04). Increasing EAT is associated with the presence of HRP, and patients with HRP have higher quantified EAT-v. The association of EAT-v with HRP is significant compared with EAT-t; however, a larger scale study is still required, and further evaluation is needed to assess whether EAT may be a potential therapeutic target for novel pharmaceutical agents. URL: https://www.crd.york.ac.uk/. Unique identifier: CRD42017055473.
| S-EPMC5586465 | biostudies-literature
Project description:Nicotinamide adenine dinucleotide (NAD+) is an essential coenzyme that regulates cellular energy metabolism in many cell types. The major purpose of the present study was to test the hypothesis that NAD+ in white adipose tissue (WAT) is a regulator of whole-body metabolic flexibility in response to changes in insulin sensitivity and with respect to substrate availability and use during feeding and fasting conditions. To this end, we first evaluated the relationship between WAT NAD+ concentration and metabolic flexibility in mice and humans. We found that WAT NAD+ concentration was increased in mice after calorie restriction and exercise, 2 enhancers of metabolic flexibility. Bariatric surgery-induced 20% weight loss increased plasma adiponectin concentration, skeletal muscle insulin sensitivity, and WAT NAD+ concentration in people with obesity. We next analyzed adipocyte-specific nicotinamide phosphoribosyltransferase (Nampt) knockout (ANKO) mice, which have markedly decreased NAD+ concentrations in WAT. ANKO mice oxidized more glucose during the light period and after fasting than control mice. In contrast, the normal postprandial stimulation of glucose oxidation and suppression of fat oxidation were impaired in ANKO mice. Data obtained from RNA-sequencing of WAT suggest that loss of NAMPT increases inflammation, and impairs insulin sensitivity, glucose oxidation, lipolysis, branched-chain amino acid catabolism, and mitochondrial function in WAT, which are features of metabolic inflexibility. These results demonstrate a novel function of WAT NAMPT-mediated NAD+ biosynthesis in regulating whole-body metabolic flexibility, and provide new insights into the role of adipose tissue NAD+ biology in metabolic health.
| S-EPMC7853299 | biostudies-literature
Project description:Background:Metabolic flexibility is the ability of cells to change substrates for energy production based on the nutrient availability and energy requirement. It has been shown that metabolic flexibility is impaired in obesity and chronic diseases such as type 2 diabetes mellitus, cardiovascular diseases, and metabolic syndrome, although, whether it is a cause or an effect of these conditions remains to be elucidated. Main body:In this paper, we have reviewed the literature on metabolic flexibility and curated pathways and processes resulting in a network resource to investigate the interplay between these processes in the subcutaneous adipose tissue. The adipose tissue has been shown to be responsible, not only for energy storage but also for maintaining energy homeostasis through oxidation of glucose and fatty acids. We highlight the role of pyruvate dehydrogenase complex-pyruvate dehydrogenase kinase (PDC-PDK) interaction as a regulatory switch which is primarily responsible for changing substrates in energy metabolism from glucose to fatty acids and back. Baseline gene expression of the subcutaneous adipose tissue, along with a publicly available obesity data set, are visualised on the cellular network of metabolic flexibility to highlight the genes that are expressed and which are differentially affected in obesity. Conclusion:We have constructed an abstracted network covering glucose and fatty acid oxidation, as well as the PDC-PDK regulatory switch. In addition, we have shown how the network can be used for data visualisation and as a resource for follow-up studies.
| S-EPMC6034334 | biostudies-literature
Project description:ContextAdipose tissue (AT) expansion occurs by hypertrophy and hyperplasia. Impaired hyperplasia, or adipogenesis, has been associated with obesity-related diseases.ObjectiveWe examined how in vivo adipogenesis in the subcutaneous abdominal (scABD) and femoral (scFEM) depots (via 8-week incorporation of deuterium) correlates with markers of metabolic health.DesignData from 52 women with obesity [27 black and 25 white; 29.7 ± 5.5 years; body mass index (BMI) 32.2 ± 2.8 kg/m2; 44.3% ± 4.0% body fat] were analyzed at Pennington Biomedical Research Center.Main outcomesA linear repeated measure model was used to assess the fraction of new adipose cells and the associated covariates. Akaike information criterion determined the covariates that best described the data. Simple associations were examined using Spearman's correlation.ResultsThe covariates that were associated with adipose kinetics included BMI, visceral AT/total abdominal AT (VAT/TAT) ratio, and the Matsuda index. Simple correlations demonstrated that adipocyte and preadipocyte formation in scABD (P = 0.02 and P = 0.16, trend, respectively) and scFEM (P = 0.01 and P = 0.24, trend, respectively) depots correlated positively with VAT/TAT. Preadipocyte and adipocyte formation in the scABD (P < 0.0001 and P = 0.02, respectively) and scFEM (P = 0.0001 and P = 0.003, respectively) was negatively associated with insulin sensitivity.ConclusionsOur results challenge the AT expandability hypothesis and suggest that higher in vivo adipose cell turnover is positively associated with BMI and VAT/TAT and negatively associated with insulin sensitivity, all correlates of impaired metabolic health.
| S-EPMC5505198 | biostudies-literature
Project description:ObjectiveThe prevalence of obesity is growing globally. Adiposity increases the risk for metabolic syndrome, type 2 diabetes and cardiovascular disease. Adipose tissue distribution influences systemic metabolism and impacts metabolic disease risk. The link between sexual dimorphisms of adiposity and metabolism is poorly defined. We hypothesise that depot-specific adipose tissue mitochondrial function contributes to the sexual dimorphism of metabolic flexibility in obesity.MethodsMale and female mice fed high fat diet (HFD) or standard diet (STD) from 8-18 weeks of age underwent whole animal calorimetry and high-resolution mitochondrial respirometry analysis on adipose tissue depots. To determine translatability we used RT-qPCR to examine key brown adipocyte-associated gene expression: peroxisome proliferator-activated receptor co-activator 1α, Uncoupling protein 1 and cell death inducing DFFA like effector a in brown adipose tissue (BAT) and subcutaneous adipose tissue (sWAT) of 18-week-old mice and sWAT from human volunteers.ResultsMale mice exhibited greater weight gain compared to female mice when challenged with HFD. Relative to increased body mass, the adipose to body weight ratio for BAT and sWAT depots was increased in HFD-fed males compared to female HFD-fed mice. Oxygen consumption, energy expenditure, respiratory exchange ratio and food consumption did not differ between males and females fed HFD. BAT mitochondria from obese females showed increased Complex I & II respiration and maximal respiration compared to lean females whereas obese males did not exhibit adaptive mitochondrial BAT respiration. Sexual dimorphism in BAT-associated gene expression in sWAT was also associated with Body Mass Index in humans.ConclusionsWe show that sexual dimorphism of weight gain is reflected in mitochondrial respiration analysis. Female mice have increased metabolic flexibility to adapt to changes in energy intake by regulating energy expenditure through increased complex II and maximal mitochondrial respiration within BAT when HFD challenged and increased proton leak in sWAT mitochondria.
| S-EPMC8310795 | biostudies-literature
Project description:Fatty acid translocase (FAT/CD36) is a transmembrane glycoprotein belonging to the scavenger class B receptor family and is encoded by the cluster of differentiation 36 (CD36) gene. This receptor has a high affinity for fatty acids and is involved in lipid metabolism. An abundance of FAT/CD36 during exercise occurs in mitochondria and solitary muscles. As such, we aimed to systematically review the evidence for the relationship FAT/CD36 and adipose tissue lipolysis during exercise training. Five electronic databases were selected for literature searches until June 2022: PubMed, Web of Science, Scopus, science direct, and Google Scholar. We combined the different synonyms and used the operators ("AND", "OR", "NOT"): (CD36 gene) OR (CD36 polymorphism) OR (cluster of differentiation 36) OR (FAT/CD36) OR (fatty acid translocase) OR (platelet glycoprotein IV) OR (platelet glycoprotein IIIb) AND (adipose tissue lipolysis) OR (fatty acids) OR (metabolism lipid) OR (adipocytes) AND (physical effort) OR (endurance exercise) OR (high-intensity training). All published cross-sectional, cohort, case-control, and randomized clinical trials investigating CD36 polymorphisms and adipose tissue lipolysis during exercise in subjects (elite and sub-elite athletes, non-athletes, sedentary individuals and diabetics), and using valid methods to measure FAT/CD36 expression and other biomarkers, were considered for inclusion in this review. We initially identified 476 publications according to the inclusion and exclusion criteria, and included 21 studies investigating FAT/CD36 and adipose tissue lipolysis during exercise in our systematic review after examination of titles, abstracts, full texts, and quality assessments using the PEDro scale. There were nine studies with male-only participants, three with female-only participants, and nine studies included both female and male participants. There were 859 participants in the 21 selected studies. Studies were classified as either low quality (n = 3), medium quality (n = 13), and high quality (n = 5). In general, the data suggests an association between FAT/CD36 and adipose tissue lipolysis during exercise training. Improvements in FAT/CD36 were reported during or after exercise in 6 studies, while there were no changes reported in FAT/CD36 in 4 studies. An association between fat oxidation and FAT/CD36 expression during exercise was reported in 7 studies. No agreement was reached in 5 studies on FAT/CD36 content after dietary changes and physical interventions. One study reported that FAT/CD36 protein expression in muscle was higher in women than in men, another reported that training decreased FAT/CD36 protein in insulin-resistant participants, while another study reported no differences in FAT/CD36 in young, trained individuals with type 2 diabetes. Our analysis shows an association between FAT/CD36 expression and exercise. Furthermore, an association between whole-body peak fat oxidation and FAT/CD36 expression during exercise training was demonstrated. Systematic Review Registration: [PROSPERO], identifier [CRD42022342455].
| S-EPMC10703436 | biostudies-literature
Project description:Nicotinamide adenine dinucleotide (NAD+) is an essential coenzyme regulating cellular energy metabolism across all species. Recent studies have shown the pleiotropic roles of adipose tissue NAD+ biology in adipose tissue and whole-body metabolism. The major purpose of the present study was to test the hypothesis that adipose tissue NAD+ biosynthesis, mediated by nicotinamide phosphoribosyltransferase (NAMPT), is a physiological regulator of whole-body metabolic flexibility. To this end, we analyzed adipocyte-specific Nampt knockout (ANKO) mice and subcutaneous white adipose tissue (WAT) biopsy samples obtained from human subjects. We found ANKO mice preferably utilized glucose substrate during the light period or after prolonged fasting. In contrast, ANKO mice had marked decreases in stimulation of glucose oxidation and suppression of fat oxidation during the postprandial status despite hyperinsulinemia. Data obtained from RNA-sequencing of WAT suggest that loss of NAMPT causes inflammation, oxidative stress, defective fatty acid oxidation, and mitochondrial dysfunction in WAT, key features of obesity and metabolic inflexibility. We also found WAT NAD+ concentration was decreased in people with obesity and insulin resistance compared with those who were non-obese and insulin-sensitive. In addition, bariatric surgery-induced 20% weight loss increased WAT NAD+ concentration in people with obesity. Taken together, our results reveal the importance of adipose tissue NAMPT-mediated NAD+ biosynthesis in regulating whole-body metabolic flexibility. Our results also provide translational and clinical insight into adipose tissue NAD+ biology in obesity and whole-body metabolic health.
2021-07-01 | GSE159397 | GEO
Project description:The purpose of this systematic review was to examine the association of metabolic syndrome (MS) with measures of benign prostatic hyperplasia (BPH) including prostate growth rate, prostate volume, International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA) level, and maximal flow rate.Medline, Cochrane CENTRAL, EMBASE, CBM, and Google Scholar databases were searched until March 23, 2015 using combinations of the keywords benign prostate hyperplasia/BPH, metabolic syndrome, total prostate volume, prostate growth rate, prostate specific antigen, International Prostate Symptom Score/IPSS, maximal flow rate. Cohort or case-control studies of patients with BPH and MS that reported quantitative outcomes were included. The pooled mean differences of the outcome measures were compared between patients with and without MS.A total of 158 potentially relevant studies were identified, and 8 were included in the meta-analysis. The 8 studies included in the meta-analysis contained a total of 3093 BPH patients, wherein 1241 had MS and 1852 did not have MS. BPH patients with MS had a significantly higher prostate growth rate (pooled mean difference?=?0.67?mL/y, P?<?0.001) and larger prostate volume (pooled mean difference?=?6.8?mL, P?=?0.010) than the BPH patients without MS. There was no significant difference in IPSS score (pooled mean difference?=?1.58, P?=?0.202) or maximal flow rate (pooled mean difference?=?-1.41?mL/s, P?=?.345) between BPH patients with and without MS. A borderline nonsignificant difference in PSA (pooled mean difference?=?0.24?ng/mL, P?=?0.056) was noted between BPH patients with and without MS.The results of this meta-analysis are consistent with literature indicating that BPH patients with MS have a higher prostate growth rate and larger prostate volume than those without MS; however, further study is necessary to determine the association of BPH and metabolic disorder elements and the potential risk of disease progression in BPH patients with MS.
| S-EPMC4902470 | biostudies-literature
Project description:The HSD11B1 gene is highly expressed in abdominal adipose tissue, and the enzyme it encodes catalyzes the interconversion of inactive cortisone to hormonally active cortisol. Genetic abnormalities of HSD11B1 have been associated with the development of abnormal glucose metabolism and body fat distribution. To systematically review studies evaluating the association of HSD11B1 gene expression in abdominal adipose tissue and HSD11B1 polymorphisms with obesity, the metabolic syndrome (MetS), and type 2 diabetes (T2DM), we conducted a search in MEDLINE, SCOPUS, and Cochrane Library databases in April 2015. The inclusion criteria were observational studies (cross-sectional, cohort, or case-control), conducted in adults, which analyzed the relationship of HSD11B1 polymorphisms and/or HSD11B1 expression in abdominal adipose tissue with obesity, MetS, or T2DM. Of 802 studies retrieved, 32 met the inclusion criteria (23 gene expression and 9 polymorphism studies). Twenty one studies analyzed the relationship between abdominal subcutaneous and/or visceral HSD11B1 expression with central and/or generalized obesity. Most studies reported that abdominal adipose HSD11B1 expression increased with increasing body mass index (15 studies) and abnormalities of glucose metabolism (7 studies), and varied with the presence of MetS (3 studies). Nine studies analyzed the association of 26 different HSD11B1 polymorphic variants with obesity, MetS, and T2DM. Only an Indian study found an association between a polymorphic variant at the HSD11B1 gene with MetS whereas in Pima Indians another polymorphic variant was found to be associated with T2DM. While the literature suggests that HSD11B1 is hyperexpressed in abdominal adipose tissue in subjects with obesity and abnormal glucose metabolism, this seems to be not true for HSD11B1 gene expression and MetS. Although an association of polymorphic variants of HSD11B1 with MetS in Indians and in the T2DM population of Pima Indians were found, most studies did not find a relationship between genetic polymorphic variants of HSD11B1 and obesity, MetS, and T2DM. Their reported conflicting and inconclusive results, suggesting that polymorphic variants of HSD11B1 may have only a small role in the development of metabolic abnormalities of susceptible populations in the development of MetS and T2DM.
| S-EPMC4459686 | biostudies-literature