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Journal of Gastrointestinal Surgery :... Feb 2022The peroxisome proliferator-activated receptor (PPAR)-γ plays a key role in adipose tissue differentiation and fat metabolism. However, it is unclear which factors may...
BACKGROUND
The peroxisome proliferator-activated receptor (PPAR)-γ plays a key role in adipose tissue differentiation and fat metabolism. However, it is unclear which factors may regulate its expression and whether obese patients have changes in adipose tissue expression of PPAR-γor potential regulators such as miR-27. Thus, our aims were to analyze PPAR-γ and miR-27 expression in adipose tissue of obese patients, and to correlate their levels with clinical variables.
SUBJECTS AND METHODS
We included 43 morbidly obese subjects who underwent sleeve gastrectomy (31 of them completed 1-year follow-up) and 19 non-obese subjects. mRNA expression of PPAR-γ1 and PPAR-γ2, miR-27a, and miR-27b was measured by qPCR in visceral and subcutaneous adipose tissue. Clinical variables and serum adipokine and hormone levels were correlated with PPAR-γ and miR-27 expression. In addition, a systematic review of the literature regarding PPAR-γ expression in adipose tissue of obese patients was performed.
RESULTS
We found no differences in the expression of PPAR-γ and miR-27 in adipose tissue of obese patients vs. controls. The literature review revealed discrepant results regarding PPAR-γ expression in adipose tissue of obese patients. Of note, we described a significant negative correlation between pre-operative PPAR-γ1 expression in adipose tissue of obese patients and post-operative weight loss, potentially linked with insulin resistance markers.
CONCLUSION
PPAR-γ1 expression in adipose tissue is associated with weight loss after sleeve gastrectomy and may be used as a biomarker for response to surgery.
Topics: Adipose Tissue; Gastrectomy; Gene Expression; Humans; MicroRNAs; Obesity, Morbid; PPAR gamma; Peroxisome Proliferator-Activated Receptors; Weight Loss
PubMed: 34882294
DOI: 10.1007/s11605-021-05216-6 -
BMC Cancer Nov 2017Colorectal cancer (CRC) is a major global public health problem and the second leading cause of cancer-related death. Mitochondrial dysfunction has long been suspected... (Review)
Review
BACKGROUND
Colorectal cancer (CRC) is a major global public health problem and the second leading cause of cancer-related death. Mitochondrial dysfunction has long been suspected to be involved in this type of tumorigenesis, as supported by an accumulating body of research evidence. However, little is known about how mitochondrial alterations contribute to tumorigenesis. Mitochondrial biogenesis is a fundamental cellular process required to maintain functional mitochondria and as an adaptive mechanism in response to changing energy requirements. Mitochondrial biogenesis is regulated by peroxisome proliferator-activated receptor gamma coactivator 1-α (PPARGC1A or PGC1α). In this paper, we report a systematic review to summarize current evidence on the role of PGC1α in the initiation and progression of CRC. The aim is to provide a basis for more comprehensive research.
METHODS
The literature search, data extraction and quality assessment were performed according to the document Guidance on the Conduct of Narrative Synthesis in Systematic Reviews and the PRISMA declaration.
RESULTS
The studies included in this review aimed to evaluate whether increased or decreased PGC1α expression affects the development of CRC. Each article proposes a possible molecular mechanism of action and we create two concept maps.
CONCLUSION
Our systematic review indicates that altered expression of PGC1α modifies CRC risk. Most studies showed that overexpression of this gene increases CRC risk, while some studies indicated that lower than normal expression levels could increase CRC risk. Thus, various authors propose PGC1α as a good candidate molecular target for cancer therapy. Reducing expression of this gene could help to reduce risk or progression of CRC.
Topics: Animals; Carcinogenesis; Colorectal Neoplasms; Evaluation Studies as Topic; Gene Expression Regulation, Neoplastic; Humans; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Risk Factors
PubMed: 29121859
DOI: 10.1186/s12885-017-3725-3 -
Oxidative Medicine and Cellular... 2021() and its ingredients (IFP) have a variety of biological activities and are widely used to treat osteoporosis (OP). Herein, we conducted a systematic review to... (Meta-Analysis)
Meta-Analysis
Antiosteoporosis Effect and Possible Mechanisms of the Ingredients of Fructus Psoraleae in Animal Models of Osteoporosis: A Preclinical Systematic Review and Meta-Analysis.
OBJECTIVE
() and its ingredients (IFP) have a variety of biological activities and are widely used to treat osteoporosis (OP). Herein, we conducted a systematic review to evaluate the efficacy of IFP for an animal model of OP from the current literatures. Potential mechanisms of IFP in the treatment of OP were also summarized.
MATERIALS AND METHODS
We carried out a search for electronic literature in the PubMed, Chinese National Knowledge Infrastructure, EMBASE, Wanfang, Web of Science, Chinese Biomedical Literature Database, and Cochrane Library, as well as Chinese VIP databases targeting articles published from inception to June 2021. The inclusion criteria were animal studies that assessed the efficacy and safety of IFP for OP, regardless of publication status or language. The exclusion criteria included (1) other types of studies (in vitro studies, case reports, clinical trials, reviews, abstracts, comments, and editorials), (2) combination with other compounds, (3) compared with other traditional Chinese medicine, (4) not osteoporosis or bone loss model, (5) studies with insufficient data, (6) lack of a control group, and (7) duplicate publications. The modified Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Stroke (CAMARADES) 10-item quality checklist was used to evaluate the risk of bias of included studies. We computed the relative risk (RR) and the standard mean difference (SMD) for dichotomous outcomes and continuous outcomes, respectively. When heterogeneity was detected or there was significant statistical heterogeneity ( < 0.05 or > 50%), a random-effects model was employed, followed by further subgroup analysis and metaregression estimations to ascertain the origins of heterogeneity. Otherwise, we used a fixed-effects model ( ≥ 0.05 or ≤ 50%). The primary outcome measures were bone mineral density (BMD), serum osteocalcin(S-OCN), bone volume over total volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp), bone maximum load, and elasticity modulus. The secondary outcome measure was the antiosteoporosis mechanisms of IFP. The STATA 12.0 software was used to analyze the data.
RESULTS
Overall, 16 studies focusing on 379 animals were enrolled into the study. The risk of bias score of included studies ranged from 4 to 7 with an average score of 5.25. The present study provided the preliminary preclinical evidence that administration of IFP could significantly increase the S-OCN, BMD, BV/TV, and Tb.N while Tb.Th and Tb.Sp were remarkably decreased by IFP in OP model animals ( < 0.05). Moreover, IFP could significantly improve the bone biomechanical indicator bone maximum load and elasticity modulus ( < 0.05). In terms of the possible mechanisms of treatment of OP, IFP exerts anti-OP effects in animal models probably through osteoprotegerin/receptor activator of the nuclear factor-B ligand/receptor activator of nuclear factor-B (OPG/RANKL/RANK), peroxisome proliferator activated receptor (PPAR-)/Axin2/Wnt, antioxidative stress via forkhead box O3a (FoxO3a)/Axin2/Wnt, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR), estrogen-like effect, and gamma-aminobutyric acid/gamma-aminobutyric acid receptor (GABA/GABARI) signaling pathway.
CONCLUSION
Taken together, the findings suggest the possibility of developing IFP as a drug or an ingredient in diet for the clinical treatment of OP. We recommend that rigorous, as well as high-quality, trials involving large sample sizes should be conducted to confirm our findings.
Topics: Animals; Fruit; Medicine, Chinese Traditional; Osteoporosis
PubMed: 34868453
DOI: 10.1155/2021/2098820 -
Current Atherosclerosis Reports Dec 2014The aim of this report is to perform a systematic review and qualitative synthesis of the literature to address whether, and to what extent, diet modulates the effects... (Review)
Review
The aim of this report is to perform a systematic review and qualitative synthesis of the literature to address whether, and to what extent, diet modulates the effects of the Pro12Ala polymorphism of peroxisome proliferator-activated receptor gamma 2 (PPARγ2) on body weight and other measures of adiposity. A systematic search of the literature was conducted, wherein both observational and experimental studies of adults were reviewed. Overall, the results of the observational studies show little consistency. Methodological differences in their design, conduct and analysis may largely account for the apparently discrepant findings. This notwithstanding, the main picture that emerges is that the energy content and composition of the diet may affect BMI, body composition and metabolic parameters in Ala allele carriers more than in Pro/Pro homozygotes. In most studies, carriers of the Ala allele with an obesogenic lifestyle (i.e. high-energy, high-carbohydrate and, to some extent, high-fat diets) are more obese than Pro homozygotes. Well-designed intervention studies with a sufficiently large sample size consistently show that carriers of the Ala allele are more prone to weight loss when exposed to a healthy lifestyle; however, these individuals do not seem to retain these benefits when returning to a sedentary lifestyle and inadequate dieting behaviours. Some key questions in this area of research have emerged. Carefully designed and adequately powered studies are needed, particularly involving the development and validation of standardized tools for the assessment of dietary exposure, including the use of biomarkers, to move the field forward.
Topics: Adult; Body Mass Index; Diet, Fat-Restricted; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Obesity; Obesity, Morbid; PPAR gamma; Phenotype; Polymorphism, Genetic; Randomized Controlled Trials as Topic; Risk Assessment; Sensitivity and Specificity; Treatment Outcome
PubMed: 25342491
DOI: 10.1007/s11883-014-0462-9 -
The Cochrane Database of Systematic... Jan 2023Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists are insulin-sensitising drugs used for the treatment of insulin resistance. In addition to lowering... (Review)
Review
BACKGROUND
Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists are insulin-sensitising drugs used for the treatment of insulin resistance. In addition to lowering glucose in diabetes, these drugs may also protect against hyperlipidaemia and arteriosclerosis, which are risk factors for stroke. This is an update of a review first published in January 2014 and subsequently updated in December 2017 and October 2019.
OBJECTIVES
To assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events for people with stroke or transient ischaemic attack (TIA).
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (1 January 2022), the Cochrane Central Register of Controlled Trials (CENTRAL; 2021, Issue 12), MEDLINE (1949 to 1 January 2022), Embase (1980 to 1 January 2022), CINAHL (1982 to 1 January 2022), AMED (1985 to 1 January 2022), and 11 Chinese databases (1 January 2022). In an effort to identify further published, unpublished, and ongoing trials, we searched ongoing trials registers, reference lists, and relevant conference proceedings, and contacted authors and pharmaceutical companies. We did not impose any language restrictions.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) evaluating PPAR-γ agonists versus placebo for the secondary prevention of stroke and related vascular events in people with stroke or TIA, with the outcomes of recurrent stroke, vascular events, and adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted eligible data, cross-checked the data for accuracy, and assessed methodological quality and risk of bias. We evaluated the certainty of evidence for each outcome using the GRADE approach.
MAIN RESULTS
We identified five RCTs with 5039 participants; two studies had a low risk of bias for all domains. Four studies evaluated the drug pioglitazone, and one study evaluated rosiglitazone. The participants in different studies were heterogeneous. Recurrent stroke Three studies evaluated the number of participants with recurrent stroke (4979 participants, a single study contributing 3876 of these). Peroxisome proliferator-activated receptor gamma agonists probably reduce the recurrence of stroke compared with placebo (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.44 to 0.99; moderate-certainty evidence). Adverse events Evidence that adverse events occurred more frequently in participants treated with PPAR-γ agonists when compared with placebo was uncertain due to wide confidence intervals and high levels of statistical heterogeneity: risk difference 10%, 95% CI -8% to 28%; low-certainty evidence). Data were available on additional composite outcomes reflecting serious vascular events (all-cause death and other major vascular events; all-cause mortality, non-fatal myocardial infarction or non-fatal stroke) from one study in 984 people. This study provided low-certainty evidence that PPAR-γ agonists led to fewer events (data not meta-analysed). Vascular events Peroxisome proliferator-activated receptor gamma agonists given over a mean duration of 34.5 months in a single trial of 984 participants may reduce serious vascular events expressed as a composite outcome of total events of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke (RR 0.73, 95% CI 0.54 to 0.99; low-certainty evidence). Other outcomes One study in 20 people measured insulin sensitivity, and one study in 40 people measured the ubiquitin-proteasome activity in carotid plaques. Our confidence in the improvements observed with PPAR-γ agonists were limited by small sample sizes and risk of bias. None of the studies reported the number of participants with disability due to vascular events or improvement in quality of life.
AUTHORS' CONCLUSIONS
Peroxisome proliferator-activated receptor gamma agonists probably reduce recurrent stroke and total events of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke, and may improve insulin sensitivity and the stabilisation of carotid plaques. Their effects on adverse events are uncertain. Our conclusions should be interpreted with caution considering the small number and the quality of the included studies. Further well-designed, double-blind RCTs with large samples are required to assess the efficacy and safety of PPAR-γ agonists in the secondary prevention of stroke and related vascular events in people with stroke or TIA.
Topics: Humans; Ischemic Attack, Transient; PPAR gamma; Insulin Resistance; Stroke; Myocardial Infarction; Randomized Controlled Trials as Topic
PubMed: 36625492
DOI: 10.1002/14651858.CD010693.pub6 -
Cureus Dec 2023This systematic review evaluates the effects of the daily intake of rosehip extract on low-density lipoprotein cholesterol (LDL-C) and blood glucose levels. It... (Review)
Review
This systematic review evaluates the effects of the daily intake of rosehip extract on low-density lipoprotein cholesterol (LDL-C) and blood glucose levels. It synthesizes findings from randomized clinical trials focusing on cardiovascular and metabolic health outcomes. The review includes studies employing various forms of rosehip supplementation, assessing primary outcomes such as LDL-C, HDL-C, total cholesterol, triglycerides, fasting blood glucose (FBG), and glycated hemoglobin (HbA1c). Secondary outcomes, such as body weight, BMI, and blood pressure, are also considered. The paper discusses the potential mechanisms of rosehip's action, including modulation of peroxisome proliferator-activated receptors and effects on various metabolic pathways. The results indicate mixed effects on lipid profiles and blood glucose levels, with some studies showing significant benefits. This review underscores the need for further research to confirm optimal dosages, treatment durations, and rosehip's efficacy in diverse populations, considering its favorable safety profile. The findings suggest the potential of rosehip extract as a complementary agent in managing cardiometabolic risk factors.
PubMed: 38283449
DOI: 10.7759/cureus.51225 -
Clinical Nutrition ESPEN Apr 2022Diabetes mellitus is one of the most important life-threatening metabolic diseases of the 21st century. The use of complementary and alternative medicine in diabetic...
BACKGROUND AND AIMS
Diabetes mellitus is one of the most important life-threatening metabolic diseases of the 21st century. The use of complementary and alternative medicine in diabetic patients seems to be increasing. Saffron, a valuable herbal medicine, has several pharmacological properties such as anti-oxidant effect, which can play important role in ameliorating the complications of diabetes. The aim of this study was to systematically review the therapeutic effects of saffron and its bioactive components on oxidative stress in diabetes mellitus.
METHODS
In this systematic review, databases such as PubMed, SCOPUS, Embase, ProQuest, and Web of Sciences were searched from the beginning to December 2021. All eligible in vitro, animal, and human studies that examined the effect of saffron on oxidative stress indices in diabetes were prepared in the form of a full article in English.
RESULTS
In the end, only 31of the 389 articles met the criteria for analysis. Of the 31 articles, 4 were in-vitro studies, 25 were animal studies, and 2 were clinical trials studies. Saffron supplementation may activate insulin receptor substrate 1 (IRS1) and peroxisome proliferator-activated receptor gamma (PPAR-γ), which can improve hyperglycemia and insulin transduction signal in adipose tissue, and regulate glucose metabolism, leading to an increased nuclear factor erythroid 2-related factor 2 (Nrf2), HO-1 expression, amelioration of mitochondrial function, and an increased levels of antioxidant enzymes.
CONCLUSION
Most studies have shown that saffron supplementation significantly enhanced the production and activity of antioxidant enzymes and decreased oxidative stress indices in diabetes mellitus. However, human pharmacokinetic and more accurate clinical trial studies are needed to determine dose ranges and the exact mechanisms of action of saffron and its active components in diabetes.
Topics: Animals; Antioxidants; Crocus; Diabetes Mellitus; Humans; Oxidative Stress; Plant Extracts
PubMed: 35331485
DOI: 10.1016/j.clnesp.2022.01.022 -
Scientific Reports Apr 2024The combination of metformin and the peroxisome proliferator-activated receptors (PPAR) agonists offers a promising avenue for managing type 2 diabetes (T2D) through... (Meta-Analysis)
Meta-Analysis
The combination of metformin and the peroxisome proliferator-activated receptors (PPAR) agonists offers a promising avenue for managing type 2 diabetes (T2D) through their potential complementary mechanisms of action. The results from randomized controlled trials (RCT) assessing the efficacy of PPAR agonists plus metformin versus metformin alone in T2D are inconsistent, which prompted the conduct of the systematic review and meta-analysis. We searched MEDLINE and EMBASE from inception (1966) to March 2023 to identify all RCTs comparing any PPAR agonists plus metformin versus metformin alone in T2D. Categorical variables were summarized as relative risk along with 95% confidence interval (CI). Twenty RCTs enrolling a total of 6058 patients met the inclusion criteria. The certainty of evidence ranged from moderate to very low. Pooled results show that using PPAR agonist plus metformin, as compared to metformin alone, results in lower concentrations of fasting glucose [MD = - 22.07 mg/dl (95% CI - 27.17, - 16.97), HbA1c [MD = - 0.53% (95% CI - 0.67, - 0.38)], HOMA-IR [MD = - 1.26 (95% CI - 2.16, - 0.37)], and fasting insulin [MD = - 19.83 pmol/L (95% CI - 29.54, - 10.13)] without significant increase in any adverse events. Thus, synthesized evidence from RCTs demonstrates the beneficial effects of PPAR agonist add-on treatment versus metformin alone in T2D patients. In particular, novel dual PPARα/γ agonist (tesaglitazar) demonstrate efficacy in improving glycaemic and lipid concentrations, so further RCTs should be performed to elucidate the long-term outcomes and safety profile of these novel combined and personalized therapeutic strategies in the management of T2D.PROSPERO registration no. CRD42023412603.
Topics: Humans; Metformin; Peroxisome Proliferator-Activated Receptors; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Drug Therapy, Combination
PubMed: 38627464
DOI: 10.1038/s41598-024-59390-z -
Nutrients Mar 2023The inter-individual variability of metabolic response to foods may be partly due to genetic variation. This systematic review aims to assess the associations between... (Review)
Review
The inter-individual variability of metabolic response to foods may be partly due to genetic variation. This systematic review aims to assess the associations between genetic variants and glucose response to an oral glucose tolerance test (OGTT). Three databases (PubMed, Web of Science, Embase) were searched for keywords in the field of genetics, OGTT, and metabolic response (PROSPERO: CRD42021231203). Inclusion criteria were available data on single nucleotide polymorphisms (SNPs) and glucose area under the curve (gAUC) in a healthy study cohort. In total, 33,219 records were identified, of which 139 reports met the inclusion criteria. This narrative synthesis focused on 49 reports describing gene loci for which several reports were available. An association between SNPs and the gAUC was described for 13 gene loci with 53 different SNPs. Three gene loci were mostly investigated: (), (), and (). In most reports, the associations were not significant or single findings were not replicated. No robust evidence for an association between SNPs and gAUC after an OGTT in healthy persons was found across the identified studies. Future studies should investigate the effect of polygenic risk scores on postprandial glucose levels.
Topics: Humans; Glucose Tolerance Test; Diabetes Mellitus, Type 2; Genotype; Risk Factors; Glucose; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease
PubMed: 37049537
DOI: 10.3390/nu15071695 -
Cardiovascular Diabetology Mar 2019Using a meta-analysis of randomized controlled trials (RCTs), this study aimed to investigate the efficacy and safety of pemafibrate, a novel selective peroxisome... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Using a meta-analysis of randomized controlled trials (RCTs), this study aimed to investigate the efficacy and safety of pemafibrate, a novel selective peroxisome proliferator-activated receptor α modulator, in patients with dyslipidemia.
METHODS
A search was performed using the MEDLINE, Cochrane Controlled Trials Registry, and ClinicalTrials.gov databases. We decided to employ RCTs to evaluate the effects of pemafibrate on lipid and glucose metabolism-related parameters in patients with dyslipidemia. For statistical analysis, standardized mean difference (SMD) or odds ratio (OR) and 95% confidence intervals (CIs) were calculated using the random effect model.
RESULTS
Our search yielded seven RCTs (with a total of 1623 patients) that satisfied the eligibility criteria of this study; hence, those studies were incorporated into this meta-analysis. The triglyceride concentration significantly decreased in the pemafibrate group (SMD, - 1.38; 95% CI, - 1.63 to - 1.12; P < 0.001) than in the placebo group, with a reduction effect similar to that exhibited by fenofibrate. Compared with the placebo group, the pemafibrate group also showed improvements in high-density and non-high-density lipoprotein cholesterol levels as well as in homeostasis model assessment for insulin resistance. Furthermore, the pemafibrate group showed a significant decrease in hepatobiliary enzyme activity compared with the placebo and fenofibrate groups; and, total adverse events (AEs) were significantly lower in the pemafibrate group than in the fenofibrate group (OR, 0.60; 95% CI, 0.49-0.73; P < 0.001). In contrast, the low-density lipoprotein cholesterol level was significantly higher in the pemafibrate group than in the placebo (P = 0.006) and fenofibrate (P < 0.001) groups.
CONCLUSIONS
The lipid profile significantly improved in the pemafibrate group than in the placebo group. In addition to the pemafibrate group having an improved lipid profile, which was comparable with that of the fenofibrate group, the AEs were significantly lower than in the fenofibrate group and an improvement in hepatobiliary enzyme activity was also recognized. However, we believe that actual clinical data as well as long-term efficacy and safety need to be investigated in the future.
Topics: Benzoxazoles; Biliary Tract; Biomarkers; Butyrates; Dyslipidemias; Female; Humans; Hypolipidemic Agents; Lipids; Liver; Male; Middle Aged; PPAR alpha; Treatment Outcome
PubMed: 30898163
DOI: 10.1186/s12933-019-0845-x