Metabolic Syndrome-related Disorders Research Articles

The Association between Functional Dyspepsia and Metabolic Syndrome-The State of the Art.

Functional dyspepsia is a common functional disorder of the gastrointestinal tract that is responsible for many primary care visits. No organic changes have been found to explain its symptoms. We hypothesize that modern lifestyles and environmental factors, especially psychological stress, play a crucial role in the high prevalence of functional dyspepsia and metabolic syndrome. While gastrointestinal tract diseases are rarely linked to metabolic disorders, chronic stress, obesity-related metabolic syndrome, chronic inflammation, intestinal dysbiosis, and functional dyspepsia have significant pathophysiological associations. Functional dyspepsia, often associated with anxiety and chronic psychological stress, can activate the neuroendocrine stress axis and immune system, leading to unhealthy habits that contribute to obesity. Additionally, intestinal dysbiosis, which is commonly present in functional dyspepsia, can exacerbate systemic inflammation and obesity, further promoting metabolic syndrome-related disorders. It is worth noting that the reverse is also true: obesity-related metabolic syndrome can worsen functional dyspepsia and its associated symptoms by triggering systemic inflammation and intestinal dysbiosis, as well as negative emotions (depression) through the brain-gut axis. To understand the pathophysiology and deliver an effective treatment strategy for these two difficult-to-cure disorders, which are challenging for both caregivers and patients, a psychosocial paradigm is essential.

Promising Influences of Moringa oleifera in Functional Foods against Metabolic Syndrome: A Comprehensive and Mechanistic Review.

Metabolic syndrome (MetS) is now considered a global issue with a growing financial and health impact. Numerous herbal alternatives have been examined and researched due to the ever-increasing demand for new medications to treat metabolic syndrome disorders. People have empirically employed Moringa oleifera (MO), a native plant to several Asian nations, for a variety of diseases. We sought to examine recent research on MO in MetS and its potential mechanism of action in the current review. Four databases, including PubMed, Scopus, Web of Sciences, and Google Scholar, were thoroughly searched, and the data were then compiled. In total, 146 papers covering nonclinical and clinical MO investigations in metabolic syndromerelated disorders are included in this study. Numerous research confirmed MO's positive impact on the control of blood glucose, blood pressure, hyperlipidemia, and obesity. Many molecular processes have been investigated, including increasing glucose transporter type 4 (GLUT4) expression, inhibition of β-Hydroxy-β-methylglutaryl-coenzyme A (HMG-CoA), α-glucosidase inhibiting, AMP-activated protein kinase (AMPK) activation, and other suggested mechanisms. The current review established much data favoring MO's potential advantages in metabolic syndrome. However, further research involving human studies is required in this area to determine whether Moringa can effectively treat metabolic syndrome.

Chronically hypertensive transgenic mice expressing human AT1R haplotype-I exhibit increased susceptibility to Francisella tularensis.

Age-related illnesses, including hypertension and accompanying metabolic disorders, compromise immunity and exacerbate infection-associated fatalities. Renin-angiotensin system (RAS) is the key mechanism that controls blood pressure. Upregulation of RAS through angiotensin receptor type 1 (AT1R), a G-protein coupled receptor, contributes to the pathophysiological consequences leading to vascular remodeling, hypertension, and end-organ damage. Genetic variations that increase the expression of human AT1R may cause the above pathological outcomes associated with hypertension. Previously we have shown that our chronically hypertensive transgenic (TG) mice containing the haplotype-I variant (Hap-I, hypertensive genotype) of human AT1R (hAT1R) gene are more prone to develop the metabolic syndrome-related disorders as compared to the TG mice containing the haplotype-II variant (Hap-II, normotensive genotype). Since aging and an increased risk of hypertension can impact multiple organ systems in a complex manner, including susceptibility to various infections, the current study investigated the susceptibility and potential effect of acute bacterial infection using a Gram-negative intracellular bacterial pathogen, Francisella tularensis in our hAT1R TG mice. Our results show that compared to Hap-II, F. tularensis-infected aged Hap-I TG mice have significantly higher mortality post-infection, higher bacterial load and lung pathology, elevated inflammatory cytokines and altered gene expression profile favoring hypertension and inflammation. Consistent with worsened phenotype in aged Hap-I mice post-Francisella infection, gene expression profiles from their lungs revealed significantly altered expression of more than 1,400 genes. Furthermore, bioinformatics analysis identified genes associated with RAS and IFN-γ pathways regulating blood pressure and inflammation. These studies demonstrate that haplotype-dependent over-expression of the hAT1R gene leads to enhanced susceptibility and lethality due to F. tularensis LVS infection, which gets aggravated in aged animals. Clinically, these findings will help in exploring the role of AT1R-induced hypertension and enhanced susceptibility to infection-related respiratory diseases.

Essential Oils: Recent Advances on Their Dual Role as Food Preservatives and Nutraceuticals against the Metabolic Syndrome.

Essential oils (EO) are compounds synthesized by plants as secondary products and are a complex mixture of volatile molecules. Studies have demonstrated their pharmacological activity in the prevention and treatment of metabolic syndrome (MetS). Moreover, they have been used as antimicrobial and antioxidant food additives. The first part of this review discusses the role of EO as nutraceuticals to prevent metabolic syndrome-related disorders (i.e., obesity, diabetes, and neurodegenerative diseases), showing results from in vitro and in vivo studies. Likewise, the second part describes the bioavailability and mechanisms of action of EO in preventing chronic diseases. The third part presents the application of EO as food additives, pointing out their antimicrobial and antioxidant activity in food formulations. Finally, the last part explains the stability and methods for encapsulating EO. In conclusion, EO dual role as nutraceuticals and food additives makes them excellent candidates to formulate dietary supplements and functional foods. However, further investigation is needed to understand EO interaction mechanisms with human metabolic pathways and to develop novel technological approaches to enhance EO stability in food systems to scale up these processes and, in this way, to overcome current health problems.

Current status of liver transplantation for non-B non-C liver cirrhosis and hepatocellular carcinoma.

Recently, non-B non-C chronic liver diseases, including alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH), have markedly increased worldwide. Liver transplantation (LT) is an effective curative therapy for hepatocellular carcinoma (HCC) as well as decompensated liver cirrhosis. In Japan, where the source of liver grafts is strongly dependent on living donors, efforts have been made to unify the indications for eligibility of HCC patients for LT, leading to the development of 5-5-500 criteria. Along with the expansion of eligibility for LT, the current changing trends in underlying liver diseases of LT recipients, which are related to the rising tide of non-B non-C cirrhosis and HCC, are highlighting the importance of peri-transplant management of patients with various comorbidities. The post-LT prognosis of patients with ALD is significantly affected by de novo malignancies and metabolic syndrome-related complications as well as posttransplant alcohol relapse. NAFLD/NASH patients often suffer from obesity, type 2 diabetes mellitus, and other metabolic syndrome-related disorders, and nonneoplastic factors such as cardiovascular events and recurrence of NAFLD/NASH have a significant impact on post-LT outcomes. Patient management in the peri-transplant period as well as risk assessment for LT are key to improving post-LT outcomes in the era of a growing number of cases of LT for non-B non-C liver diseases.

Contemporary trends in the surgical management of urinary incontinence after radical prostatectomy in the United States.

To identify trends, costs, and predictors in the use of different surgical procedures for post-radical prostatectomy incontinence (PPI). We identified 21,589 men who were diagnosed with localized prostate cancer (PCa) and treated with radical prostatectomy (RP) from 2003 to 2017. The primary outcome was the incontinence procedure performances. Optum's de-identified Clinformatics® Data Mart Database was queried to define the cohort of interest. The average costs of the different incontinence procedures were obtained and compared. Also, demographic, and clinical predictors of incontinence surgery were evaluated by multivariable regression analysis. Of the 21,589 men with localized PCa treated with RP, 740 (3.43%) underwent at least one incontinence procedure during a median of 5 years of follow-up. In total, there were 844 unique incontinence procedures. Male slings were the most common procedure (47.5%), had an intermediate cost compared to the other treatment options, and was the first-choice treatment for the majority of patients (50%). The use of an artificial urinary sphincter (AUS) was the second most common (35.3%), but also was the most expensive treatment and was first-choice-treatment for 32.3% of patients. On multivariable analysis, metabolic syndrome related disorders, adjuvant/salvage radiation therapy as well as a history of neurological comorbidities were independently associated with an increased likelihood of incontinence surgery. The receipt of male slings increased and then subsequently decreased, while AUS utilization was stable, and the use of urethral bulking agents was uncommon. From a cost standpoint, AUS was the most expensive option. Finally, patient's comorbidity history and RP related factors were found to influence the choice for primary or subsequent PPI interventions.

Metabolic-Syndrome-Related Comorbidities in Narcolepsy Spectrum Disorders: A Preliminary Cross-Sectional Study in Japan.

Narcolepsy types 1 (NT1) and 2 (NT2) and idiopathic hypersomnia (IH) are thought to be a disease continuum known as narcolepsy spectrum disorders (NSDs). This study aimed to assess the prevalence of and factors associated with metabolic-syndrome-related disorders (MRDs) among patients with NSD. Japanese patients with NSD (NT1, n = 94; NT2, n = 83; and IH, n = 57) aged ≥35 years were enrolled in this cross-sectional study. MRD was defined as having at least one of the following conditions: hypertension, diabetes, or dyslipidemia. Demographic variables and MRD incidence were compared among patients in the respective NSD categories. Multivariate logistic regression analysis was used to investigate the factors associated with MRDs. Patients with NT1 had a higher body mass index (BMI) and incidence of MRD than that had by those with NT2 or IH. Age, BMI, and the presence of OSA were significantly associated with the incidence of MRD in NSDs. Age and BMI in NT1, BMI and human leukocyte antigen (HLA)-DQB1*06:02 positivity in NT2, and only age in IH were factors associated with the incidence of MRD. Obesity should be carefully monitored in narcolepsy; however, NT2 with HLA-DQB1*06:02 positive should be followed up for the development of MRD even without obesity.

Metabolic Environment Alters the Transcriptomic Landscape of the Aged Heart

Eating disorders at older age are coupled with a number of unfavorable health outcomes, including cardiovascular disease; but mechanisms underlying the process remain to be clarified. For this purpose, we studied alterations in gene expression profile of hearts from aged mice following exposure to Western diet. Specifically, we used transgenic mice expressing the haplotype-I (Hap-I: hypertensive genotype) of the human angiotensin receptor type 1 (AT1R) gene because these animals are more prone to develop metabolic syndrome-related disorders. For comparison, mice containing haplotype-II of human AT1R (Hap-II: normotensive genotype) were used. Aged mice (20-24 months of age) were maintained on a regular diet or high fat diet with 2% NaCl (Western diet) for 16 weeks. Blood pressure was monitored by telemetry, whereas cardiac anatomy and gene expression profile were established on heart specimens, using histological and RNA-seq analysis. On regular diet, old Hap-I mice presented higher (~9 mmHg) systolic blood pressure, with respect to aged-matched Hap-II animals. Following administration of Wester diet, blood pressure increased in both groups of mice, but to a larger extent in Hap-I animals (~15 mmHg), in comparison to Hap-II (~7 mmHg). With respect to Hap-II, aged Hap-I mice on regular diet tended to have larger heart weight-to-body weight ratio, increased cell size, and higher levels of fibrosis. Western Diet treatment exacerbated these differences. RNA sequencing data from cardiac tissue of Hap-I aged mice revealed that Western diet significantly altered the expression of >500 genes (p-adj. <0.05). Bioinformatics analysis, using Qiagen IPA software, identified major alterations in main canonical pathways involved in cardiac function, inflammation, and oxidative damage. Top hits in the disease and biological function category included arrhythmia, chamber enlargement, and cell death. Importantly, IRF3, IRF7, IFNG and STAT1 were among the top upstream regulators significantly affected by Western diet. Overall, these results indicate that Western diet promotes hypertension, hypertrophy, and fibrosis in the heart of aged mice. These alterations are paralleled by perturbation of cardiac transcriptional profile, including upstream gene regulators.

Myosteatosis in NAFLD patients correlates with plasma Cathepsin D.

Previously, we have shown that hepatic lipid accumulation induces the secretion of cathepsin D (CTSD), and that plasma CTSD levels are associated with increased inflammation and disease severity in nonalcoholic fatty liver disease (NAFLD). Although it is clear that the liver is a major source of plasma CTSD, it is unknown whether other metabolically active organs such as the muscle, also associate with plasma CTSD levels in NAFLD patients. Therefore, the aim of this study was to explore the relation between lipid accumulation in the muscle (myosteatosis) and plasma CTSD levels in forty-five NAFLD patients. We observed that hepatic steatosis positively associated with plasma CTSD levels, confirming the previously established link between plasma CTSD and the liver. Furthermore, a positive association between myosteatosis and plasma CTSD levels was observed, which was independent of sex, age, BMI, waist circumference and hepatic steatosis. By establishing a positive association between myosteatosis and plasma CTSD levels, our findings suggest that, in addition to the liver, the muscle is also linked to plasma CTSD levels in NAFLD patients. The observed link between myosteatosis and plasma CTSD levels supports the concept of a significant role of the skeletal muscle in metabolic disturbances in metabolic syndrome-related disorders.

The impact of Helicobacter pylori infection on gut microbiota-endocrine system axis; modulation of metabolic hormone levels and energy homeostasis.

The gut microbiota is a complex ecosystem that is involved in the development and preservation of the immune system, energy homeostasis and nutritional status of the host. The crosstalk between gut microbiota and the host cells modulates host physiology and metabolism through different mechanisms. Helicobacter pylori (H. pylori) is known to reside in the gastric mucosa, induce inflammation, and alter both gastric and intestinal microbiota resulting in a broad spectrum of diseases, in particular metabolic syndrome-related disorders. Infection with H. pylori have been shown to affect production level and physiological regulation of the gut metabolic hormones such as ghrelin and leptin which are involved in food intake, energy expenditure and body mass. In this study, we reviewed and discussed data from the literature and follow-up investigations that links H. pylori infection to alterations of the gut microbiota and metabolic hormone levels, which can exert broad influences on host metabolism, energy homeostasis, behavior, appetite, growth, reproduction and immunity. Also, we discussed the strong potential of fecal microbiota transplantation (FMT) as an innovative and promising investigational treatment option for homeostasis of metabolic hormone levels to overcome H. pylori-associated metabolic syndrome-related disorders.

MiR-103/107 promote ER stress-mediated apoptosis via targeting the Wnt3a/β-catenin/ATF6 pathway in preadipocytes

Both miR-103 and miR-107 have been demonstrated to restrain cell proliferation and regulate lipid metabolism and inflammation. However, the effects of miR-103/107 on preadipocyte apoptosis remain unknown. In the present research, we have investigated how miR-103/107 regulated preadipocyte apoptosis. We found that miR-103/107 aggravated endoplasmic reticulum (ER) stress-mediated apoptosis in preadipocytes. We confirmed that miR-103/107 targeted WNT family member 3a (Wnt3a) in preadipocytes. It was found that overexpressing Wnt3a resulted in suppression of ER stress-mediated apoptosis, while restoration of miR-103/107 counteracted the effects of Wnt3a in preadipocytes. Moreover, bioinformatics and luciferase assays indicated that activating transcription factor (ATF)6 is a key player linking miR-103/107-induced ER stress to apoptosis. ATF6 is regulated by lymphoid enhancer-binding factor 1, a transcription factor downstream of the Wnt3a/β-catenin signaling pathway, and ATF6 binds to the B-cell lymphoma 2 (Bcl2) promoter to regulate apoptosis further. In conclusion, miR-103/107 promoted ER stress-mediated apoptosis by targeting the Wnt3a/β-catenin/ATF6 signaling pathway in preadipocytes. This study revealed that the miR-103/107-Wnt3a/β-catenin-ATF6 pathway is critical to the progression of apoptosis in preadipocytes, which suggested that approaches to activate miR-103/107 could potentially be useful as new therapies for treating obesity and metabolic syndrome-related disorders.

Early and Late Postnatal Accelerated Growth Have Distinct Effects on Metabolic Health in Normal Birth Weight Infants.

Accelerated growth in postnatal life in low birth weight infants has been associated with insulin resistance and metabolic syndrome-related disorders in later life. Postnatal accelerated growth in also common in normal birth weight infants, but little is known about the impact on metabolic health. In a prospective cohort study of 203 term normal birth weight infants, we evaluated the impacts of accelerated (Δweight Z score > 0.5) or decelerated (Δweight ΔZ < −0.5) growth during early (0–3 months) and late (3–12 months) postnatal life on metabolic health indicators at age 1-year. The primary outcomes were homeostasis model assessment of insulin resistance (HOMA-IR), β-cell function [homeostasis model assessment of β-cell function (HOMA-β)], and fasting plasma lipids. Adjusting for maternal, paternal, and infant characteristics, accelerated growth during the first 3 months of life was associated with a 41.6% (95% confidence interval 8.9–84.2%) increase in HOMA-β, and a 8.3% (0.7–15.4%) decrease in fasting plasma total cholesterols, and was not associated with HOMA-IR in infants at age 1-year. Accelerated growth during 3–12 months was associated with a 30.9% (3.3–66.0%) increase in HOMA-IR and was not associated with HOMA-β. Neither accelerated nor decelerated growth was associated with fasting plasma triglycerides, high-density lipoprotein or low-density lipoprotein cholesterol concentrations in infants at age 1-year. Accelerated growth during early postnatal life may be beneficial for β-cell function, but during late postnatal life harmful for insulin sensitivity in normal birth weight infants.

Role of brown adipose tissue in the pathogenesis of metabolic syndrome

Aim: Recent studies dealing with metabolic syndrome (MS) and related complications has been focused on brown adipose tissue (BAT), because depots of this tissue has been lately found in adult humans and because of its ability to degrade energetic substrates. However, the exact role of BAT in the pathogenesis of MS remains unclear. Here we study age-related changes of interscapular BAT (iBAT) activity of non-obese model of dyslipidemia and metabolic syndrome - hereditary hypertriglyceridemic rats (HHTg) in comparison with control rats Wistar. We further analyzed the effect iBAT extirpation on metabolic syndrome-related disorders.

Short-chain fatty acids and inulin, but not guar gum, prevent diet-induced obesity and insulin resistance through differential mechanisms in mice

The role of dietary fibre and short-chain fatty acids (SCFA) in obesity development is controversially discussed. Here, we investigated how various types of dietary fibre and different SCFA ratios affect metabolic syndrome-related disorders. Male mice (B6) were fed high-fat diets supplemented with dietary fibres (either cellulose, inulin or guar gum) or different Ac:Pr ratios (high acetate (HAc) or propionate (HPr)) for 30 weeks. Body-fat gain and insulin resistance were greatly reduced by inulin, but not by guar gum, and completely prevented by SCFA supplementation. Only inulin and HAc increased body temperature, possibly by the induction of beige/browning markers in WAT. In addition, inulin and SCFA lowered hepatic triglycerides and improved insulin sensitivity. Both, inulin and HAc reduced hepatic fatty acid uptake, while only inulin enhanced mitochondrial capacity and only HAc suppressed lipogenesis in liver. Interestingly, HPr was accompanied by the induction of Nrg4 in BAT. Fermentable fibre supplementation increased the abundance of bifidobacteria; B. animalis was particularly stimulated by inulin and B. pseudolongum by guar gum. We conclude that in contrast to guar gum, inulin and SCFA prevent the onset of diet-induced weight gain and hepatic steatosis by different mechanisms on liver and adipose tissue metabolism.

The molecular structure of thio-ether fatty acids influences PPAR-dependent regulation of lipid metabolism

Thio-ether fatty acids (THEFAs), including the parent 2-(tetradecylthio)acetic acid (TTA), are modified fatty acids (FAs) that have profound effects on lipid metabolism given that they are blocked for β-oxidation, and able to act as peroxisome proliferator-activated receptor (PPAR) agonists. Therefore, TTA in particular has been tested clinically for its therapeutic potential against metabolic syndrome related disorders. Here, we describe the preparation of THEFAs based on the TTA scaffold with either a double or a triple bond. These are tested in cultured human skeletal muscle cells (myotubes), either as free acid or following esterification as phospholipids, lysophospholipids or monoacylglycerols. Metabolic effects are assessed in terms of cellular bioavailabilities in myotubes, by FA substrate uptake and oxidation studies, and gene regulation studies with selected PPAR-regulated genes. We note that the inclusion of a triple bond promotes THEFA-mediated FA oxidation. Furthermore, esterification of THEFAs as lysophospholipids also promotes FA oxidation effects. Given that the apparent clinical benefits of TTA administration were offset by dose limitation and poor bioavailability, we discuss the possibility that a selection of our latest THEFAs and THEFA-containing lipids might be able to fulfill the therapeutic potential of the parent TTA while minimizing required doses for efficacy, side-effects and adverse reactions.

Long Noncoding RNAs in Metabolic Syndrome Related Disorders.

Ribonucleic acids (RNAs) are very complex and their all functions have yet to be fully clarified. Noncoding genes (noncoding RNA, sequences, and pseudogenes) comprise 67% of all genes and they are represented by housekeeping noncoding RNAs (transfer RNA (tRNA), ribosomal RNA (rRNA), small nuclear RNA (snRNA), and small nucleolar RNA (snoRNA)) that are engaged in basic cellular processes and by regulatory noncoding RNA (short and long noncoding RNA (ncRNA)) that are important for gene expression/transcript stability. In this review, we summarize data concerning the significance of long noncoding RNAs (lncRNAs) in metabolic syndrome related disorders, focusing on adipose tissue and pancreatic islands.

Perinatal Oxidative Stress May Affect Fetal Ghrelin Levels in Humans.

In vitro cell model studies have shown that oxidative stress may affect beta-cell function. It is unknown whether oxidative stress may affect metabolic health in human fetuses/newborns. In a singleton pregnancy cohort (n = 248), we studied maternal (24–28 weeks gestation) and cord plasma biomarkers of oxidative stress [malondialdehyde (MDA), F2-isoprostanes] in relation to fetal metabolic health biomarkers including cord plasma glucose-to-insulin ratio (an indicator of insulin sensitivity), proinsulin-to-insulin ratio (an indicator of beta-cell function), insulin, IGF-I, IGF-II, leptin, adiponectin and ghrelin concentrations. Strong positive correlations were observed between maternal and cord plasma biomarkers of oxidative stress (r = 0.33 for MDA, r = 0.74 for total F2-isoprostanes, all p < 0.0001). Adjusting for gestational age at blood sampling, cord plasma ghrelin concentrations were consistently negatively correlated to oxidative stress biomarkers in maternal (r = −0.32, p < 0.0001 for MDA; r = −0.31, p < 0.0001 for F2-isoprostanes) or cord plasma (r = −0.13, p = 0.04 for MDA; r = −0.32, p < 0.0001 for F2-isoprostanes). Other fetal metabolic health biomarkers were not correlated to oxidative stress. Adjusting for maternal and pregnancy characteristics, similar associations were observed. Our study provides the first preliminary evidence suggesting that oxidative stress may affect fetal ghrelin levels in humans. The implications in developmental “programming” the vulnerability to metabolic syndrome related disorders remain to be elucidated.

Maternal Smoking and Metabolic Health Biomarkers in Newborns.

BackgroundMaternal smoking has been associated with elevated risk of type 2 diabetes among the offspring in adulthood. The mechanisms underlying this fetal “programming” effect remain unclear. The present study sought to explore whether maternal smoking affects metabolic health biomarkers in fetuses/newborns.MethodsIn a prospective singleton pregnancy cohort (n = 248), we compared metabolic health biomarkers in the newborns of smoking and non-smoking mothers. Outcomes included cord plasma insulin, proinsulin, insulin-like growth factor I (IGF-I), IGF-II, leptin and adiponectin concentrations, glucose-to-insulin ratio (an indicator of insulin sensitivity) and proinsulin-to-insulin ratio (an indicator of β-cell function).ResultsIndependent of maternal (glucose tolerance, age, ethnicity, parity, education, body mass index, alcohol use) and infant (sex, gestational age, birth weight z score, mode of delivery, cord blood glucose concentration) characteristics, the newborns of smoking mothers had lower IGF-I concentrations (mean: 6.7 vs. 8.4 nmol/L, adjusted p = 0.006), and marginally higher proinsulin-to-insulin ratios (0.94 vs. 0.72, adjusted p = 0.06) than the newborns of non-smoking mothers. Cord plasma insulin, proinsulin, IGF-II, leptin and adiponectin concentrations and glucose-to-insulin ratios were similar in the newborns of smoking and non-smoking mothers.ConclusionsMaternal smoking was associated with decreased fetal IGF-I levels, and borderline lower fetal β-cell function. Larger cohort studies are required to confirm the latter finding. The preliminary findings prompt the hypothesis that these early life metabolic changes may be involved in the impact of maternal smoking on future risk of metabolic syndrome related disorders in the offspring.

Positive effects of voluntary running on metabolic syndrome-related disorders in non-obese hereditary hypertriacylglycerolemic rats.

While metabolic syndrome is often associated with obesity, 25% of humans suffering from it are not obese and the effect of physical activity remains unclear in such cases. Therefore, we used hereditary hypertriaclyglycerolemic (HHTg) rats as a unique model for studying the effect of spontaneous physical activity [voluntary running (VR)] on metabolic syndrome-related disorders, such as dyslipidemia, in non-obese subjects. Adult HHTg males were fed standard (CD) or high-sucrose (HSD) diets ad libitum for four weeks. Within both dietary groups, some of the rats had free access to a running wheel (CD+VR, HSD+VR), whereas the controls (CD, HSD) had no possibility of extra physical activity. At the end of the four weeks, we measured the effects of VR on various metabolic syndrome-associated parameters: (i) biochemical parameters, (ii) the content and composition of triacylglycerols (TAG), diacylglycerols (DAG), ceramides and membrane phospholipids, and (iii) substrate utilization in brown adipose tissue. In both dietary groups, VR led to various positive effects: reduced epididymal and perirenal fat depots; increased epididymal adipose tissue lipolysis; decreased amounts of serum TAG, non-esterified fatty acids and insulin; a higher insulin sensitivity index. While tissue ceramide content was not affected, decreased TAG accumulation resulted in reduced and modified liver, heart and skeletal muscle DAG. VR also had a beneficial effect on muscle membrane phospholipid composition. In addition, compared with the CD group, the CD+VR rats exhibited increased fatty acid oxidation and protein content in brown adipose tissue. Our results confirm that physical activity in a non-obese model of severe dyslipidemia has many beneficial effects and can even counteract the negative effects of sucrose consumption. Furthermore, they suggest that the mechanism by which these effects are modulated involves a combination of several positive changes in lipid metabolism.

Carnitine supplementation alleviates lipid metabolism derangements and protects against oxidative stress in non-obese hereditary hypertriglyceridemic rats.

The aim of this study was to estimate the effect of carnitine supplementation on lipid disorders and peripheral tissue insulin sensitivity in a non-obese animal model of insulin resistance, the hereditary hypertriglyceridemic (HHTg) rat. Male HHTg rats were fed a standard diet, and half of them received daily doses of carnitine (500 mg·kg(-1) body weight) for 8 weeks. Rats of the original Wistar strain were used for comparison. HHTg rats exhibited increased urinary excretion of free carnitine and reduced carnitine content in the liver and blood. Carnitine supplementation compensated for this shortage and promoted urinary excretion of acetylcarnitine without any signs of (acyl)carnitine accumulation in skeletal muscle. Compared with their untreated littermates, carnitine-treated HHTg rats exhibited lower weight gain, reduced liver steatosis, lower fasting triglyceridemia, and greater reduction of serum free fatty acid content after glucose load. Carnitine treatment was associated with increased mitochondrial biogenesis and oxidative capacity for fatty acids, amelioration of oxidative stress, and restored substrate switching in the liver. In skeletal muscle (diaphragm), carnitine supplementation was associated with significantly higher palmitate oxidation and a more favorable complete to incomplete oxidation products ratio. Carnitine supplementation further enhanced insulin sensitivity ex vivo. No effects on whole-body glucose tolerance were observed. Our data suggest that some metabolic syndrome-related disorders, particularly fatty acid oxidation, steatosis, and oxidative stress in the liver, could be attenuated by carnitine supplementation. The effect of carnitine could be explained, at least partly, by enhanced substrate oxidation and increased fatty acid transport from tissues in the form of short-chain acylcarnitines.