Visceral Fat Accumulation Research Articles

Higher levels of serum α-Klotho are longitudinally associated with less central obesity in girls experiencing weight gain.

Klotho is an anti-aging protein that reduces adiposity and increases caloric expenditure, among others. Although associations between secreted α-Klotho levels and obesity have been described, its relationship with central obesity and visceral fat accumulation during childhood is poorly understood. Our objective was to study the longitudinal associations between serum α-Klotho concentrations and obesity-related parameters in apparently healthy children. We studied a cohort of 208 apparently healthy school-age children (107 girls and 101 boys) assessed at baseline (mean age 8.5 ± 1.8 years) and at follow-up 4 years later. Serum α-Klotho concentrations were measured at baseline in all subjects. Obesity-related parameters, such as BMI, waist circumference, body fat, visceral fat, triglyceride levels, HOMA-IR index, and C-reactive protein were studied. Boys and girls were classified into 3 groups according to weight change between baseline and follow-up visits: weight loss, stable weight, or weight gain (based on a BMI-SDS change cut-off > 0.35 SD). In girls (N=107), but not in boys, we observed negative associations of serum α-Klotho protein with BMI, waist circumference, body fat, visceral fat, HOMA IR index, and C-reactive protein at baseline and also at follow-up. The associations of α-Klotho and obesity-related parameters were more evident in girls who exhibited weight gain. In such girls, multivariate regression analyses (adjusting for age, puberty and baseline weight/height ratio) showed that α-Klotho protein was negatively associated with follow-up BMI, waist circumference, and visceral fat (p = 0.003 to 0.028). For each 1 SD-increase in baseline α-Klotho, follow-up waist circumference decreased by 4.15 cm and visceral fat by 1.38 mm. In school-age girls, serum α-Klotho concentrations are longitudinally related to a more favorable metabolic profile. In girls experiencing weight gain, α-Klotho may prove to be a protective factor against the accumulation of visceral fat.

Pancreatic β-Cell Apoptosis in Normoglycemic Rats is Due to Mitochondrial Translocation of p53-Induced by the Consumption of Sugar-Sweetened Beverages.

Overstimulation of pancreatic β-cells can lead to dysfunction and death, prior to the clinical manifestations of type 2 diabetes (T2D). The excessive consumption of carbohydrates induces metabolic alterations that can affect the functions of the β-cells and cause their death. We analyzed the role of p53 in pancreatic β cell death in carbohydrate-supplemented Sprague Dawley rats. For four months, the animals received drinking water containing either 40% sucrose or 40% fructose. The glucose tolerance test was performed at week 15. Apoptosis was assessed with the TUNEL assay (TdT-mediated dUTP-nick end-labeling). Bax, p53, and insulin were assessed by Western blotting, immunofluorescence, and real-time quantitative PCR. Insulin, triacylglycerol, and serum glucose and fatty acids in pancreatic tissue were measured. Carbohydrate consumption promotes apoptosis and mobilization of p53 from the cytosol to rat pancreatic β-cell mitochondria before blood glucose rises. An increase in p53, miR-34a, and Bax mRNA was also detected (P < 0.001) in the sucrose group. As well as hypertriglyceridemia, hyperinsulinemia, glucose intolerance, insulin resistance, visceral fat accumulation, and increased pancreatic fatty acids in the sucrose group. Carbohydrate consumption increases p53 and its mobilization into β-cell mitochondria and coincides with the increased rate of apoptosis, which occurs before serum glucose levels rise.

Loss of epidermal glucocorticoid receptor protects against whole body metabolic dysfunction upon chronic corticosterone treatment

ObjectiveGlucocorticoid (GC) excess contributes to the development of metabolic syndrome, defined by visceral obesity, abnormal glucose tolerance, and dyslipidemia. While it is accepted that loss of metabolic control is causative of cutaneous diseases, the systemic effects of epidermal dysfunction have received limited attention. Importantly, independent of GC blood levels, skin synthesis of these hormones can provide tissue-specific variations that may affect global homeostasis. We aimed to assess whether the epidermal-specific loss of the GC receptor (GR) had an impact on the dermal white adipose tissue (dWAT), a specialized fat depot functionally different from other fat pads, as well as on whole body homeostasis. MethodsGR epidermal KO (GREKO) and control female mice were treated with oral corticosterone (CORT) for 4 weeks, a protocol inducing metabolic dysfunction. Metabolic parameters including body weight, visceral and hepatic fat accumulation, blood glucose and insulin levels, glucose tolerance tests upon fasting, and triglycerides levels, were determined. Systemic alterations of soluble factors with known roles in immunity and inflammation were also assessed by a multiplex antibody array system containing selected cytokines, chemokines, and growth factors. The levels of cutaneous GCs and the profile of skin-secreted factors were determined in tissue explants by ELISA and the multiplex array system. Morphometric studies quantitated changes in dWAT thickness and adipocyte size in both genotypes, basally and at the end of CORT treatment. The expression of adipocyte markers was assessed in purified dermal adipocytes in vehicle and CORT-treated GREKOvs controls. ResultsDespite similar circulating levels of GCs, GREKO mice were highly resistant to CORT-induced systemic metabolic anomalies including body weight gain, visceral and hepatic fat, hyperglycemia, insulinemia, and elevated levels of plasma triglycerides, leptin, FGF-21, PAI-1, and CCL11. GREKO mice featured constitutively enhanced levels of cutaneous GCs relative to controls at least partially due to keratinocyte-specific increased expression of the critical steroidogenic enzyme Cyp11b1. Also, the higher ratio of skin-secreted protective vs inflammatory adipokines in GREKOvs controls, correlated with higher capacity of adipogenic conversion in experiments using conditioned media from tissue explants. Following CORT treatment, relative to controls, GREKO mice featured reduced dWAT hyperplasia and adipocyte hypertrophy, with increased Adipoq and decreased Lipocalin 2 expression in purified dermal adipocytes. ConclusionsOverall data suggest that epidermal GR loss results in paracrine actions on dermal adipocytes as well as endocrine actions on key metabolic tissues that significantly improve the whole body metabolism in a mouse model of metabolic dysfunction.

Role and mechanism of FLT4 in high-fat diet-induced obesity in mice

The FLT4 gene plays an important role in the onset and progression of obesity and is involved in the structure and function of lymphatic vessels. By inducing a mouse obesity model with a high-fat diet and knocking out the FLT4 gene, which is associated with lymphatic vessel growth in mice, FLT4+/− mice were found to be susceptible to high-fat diet-induced obesity, with significant accumulation of visceral fat. BODIPY™ FL C16 imaging revealed dilated and branched mesenteric lymphatic vessels in FLT4+/− mice. Immunofluorescence staining showed that FLT4+/− exacerbated the morphological abnormalities of lymphatic vessels and submucosal lymphatic vessels in visceral adipose tissue of obese mice, accompanied by macrophage infiltration around lymphatic vessels. In addition, FLT4 knock down increased the proportion of M1-type macrophages in the adipose tissue of the epididymis, indicating significant chronic inflammation in FLT4+/− obese mice. These findings provide new evidence for the involvement of lymphatic vessel morphological abnormalities in the onset and progression of obesity and highlight the importance of further investigation of FLT4 to better understand the mechanism of HFD-induced obesity and to develop related treatments.

The Transcriptomic Landscape of Age-Induced Changes in Human Visceral Fat and the Predicted Omentum-Liver Connectome in Males.

Aging causes alterations in body composition. Specifically, visceral fat mass increases with age and is associated with age-related diseases. The pathogenic potential of visceral fat accumulation has been associated with its anatomical location and metabolic activity. Visceral fat may control systemic metabolism by secreting molecules that act in distal tissues, mainly the liver, through the portal vein. Currently, little is known about age-related changes in visceral fat in humans. Aiming to identify molecular and cellular changes occurring with aging in the visceral fat of humans, we analyzed publicly available transcriptomic data of 355 omentum samples from the Genotype-Tissue Expression portal (GTEx) of 20-79-year-old males and females. We identified the functional enrichment of genes associated with aging, inferred age-related changes in visceral fat cellularity by deconvolution analysis, profiled the senescence-associated secretory phenotype of visceral adipose tissue, and predicted the connectivity of the age-induced visceral fat secretome with the liver. We demonstrate that age induces alterations in visceral fat cellularity, synchronous to changes in metabolic pathways and a shift toward a pro-inflammatory secretory phenotype. Furthermore, our approach identified candidates such as ADIPOQ-ADIPOR1/ADIPOR2, FCN2-LPR1, and TF-TFR2 to mediate visceral fat-liver crosstalk in the context of aging. These findings cast light on how alterations in visceral fat with aging contribute to liver dysfunction and age-related disease etiology.

Comprehensive effects of lifestyle reform, adherence, and related factors on hypertension control: A review.

Despite the effectiveness of currently available antihypertensive medications, there is still a need for new treatment strategies that are more effective in certain groups of hypertensive and for additional resources to combat hypertension. However, medication non-adherence was previously recognized as a major problem in the treatment of hypertension. The mechanisms behind the positive impacts of lifestyle changes might occur in different ways. In comparison with other studies, the efficacy and effectiveness of lifestyle modifications and antihypertensive pharmaceutical treatment for the prevention and control of hypertension and concomitant cardiovascular disease have been demonstrated in randomized controlled trials. However, in this review, the attitudinal lifestyle modifications and barriers to blood pressure control were elaborated on. An effective method for reducing blood pressure (BP) and preventing cardiovascular events with antihypertensive medications has been outlined. Maintaining healthy lifestyle factors (body mass index, diet, smoking, alcohol consumption, sodium excretion, and sedentary behavior) could lower systolic blood pressure BP by 3.5 mm Hg and reduce the risk of cardiovascular disease (CVD) by about 30%, regardless of genetic susceptibility to hypertension. Conducting a lifestyle intervention using health education could improve lifestyle factors, such as reducing salt, sodium, and fat intake, changing eating habits to include more fruits and vegetables, not smoking, consuming less alcohol, exercising regularly, maintaining healthy body weight, and minimizing stressful conditions. Each behavior could affect BP by modulating visceral fat accumulation, insulin resistance, the renin-angiotensin-aldosterone system, vascular endothelial function, oxidative stress, inflammation, and autonomic function. Evidence of the joint effect of antihypertensive medications and lifestyle reforms suggests a pathway to reduce hypertension.

Pyrroloquinoline-quinone to reduce fat accumulation and ameliorate obesity progression.

Obesity is a major health concern worldwide, and its prevalence continues to increase in several countries. Pyrroloquinoline quinone (PQQ) is naturally found in some foods and is available as a dietary supplement in its disodium crystal form. The potential health benefits of PQQ have been studied, considering its antioxidant and anti-inflammatory properties. Furthermore, PQQ has been demonstrated to significantly influence the functions of mitochondria, the organelles responsible for energy production within cells, and their dysfunction is associated with various health conditions, including obesity complications. Here, we explore PQQ properties that can be exploited in obesity treatment and highlight the underlying molecular mechanisms. We review animal and cell culture studies demonstrating that PQQ is beneficial for reducing the accumulation of visceral and hepatic fat. In addition to inhibiting lipogenesis, PQQ can increase mitochondria number and function, leading to improved lipid metabolism. Besides diet-induced obesity, PQQ ameliorates programing obesity of the offspring through maternal supplementation and alters gut microbiota, which reduces obesity risk. In obesity progression, PQQ mitigates mitochondrial dysfunction and obesity-associated inflammation, resulting in the amelioration of the progression of obesity co-morbidities, including non-alcoholic fatty liver disease, chronic kidney disease, and Type 2 diabetes. Overall, PQQ has great potential as an anti-obesity and preventive agent for obesity-related complications. Although human studies are still lacking, further investigations to address obesity and associated disorders are still warranted.

Impact of Abdominal Fat Distribution on Mortality and Its Changes Over Time in Patients Undergoing Hemodialysis: A Prospective Cohort Study

Measures of fat distribution and visceral fat accumulation maintain a direct association with mortality in the general population. However, among patients undergoing hemodialysis (HD), there are few reports of this association. This study aimed to investigate the impact of computed tomography (CT)-measured abdominal fat levels, including the visceral fat area (VFA) and subcutaneous fat area (SFA), on all-cause mortality in patients undergoing HD and investigate whether there are sex-specific particularities regarding the associations between the abovementioned parameters. A total of 258 participants were selected from the population of patients undergoing stable HD. The baseline characteristics were collected by records and interviews. The following variables were assessed at baseline and every year: body mass index, abdominal circumference, VFA, and SFA. Abdominal circumference and body fat distribution were assessed at the level of the umbilicus via CT. All CT scans were performed on a nondialysis day with the subject in a supine position. The primary end point was the 5-year all-cause mortality. This prospective cohort study revealed that age, cardiothoracic ratio, %VFA (VFA/[VFA+SFA]), and albumin were independent predictors of death via multivariable analyses. Regarding the %VFA, its area under the curve (0.599), which did not suffice to predict mortality, was higher than that of VFA, SFA, and body mass index. Also, the effect was recognized mainly in male patients. The %VFA of patients who survived for 60months increased over time. These data suggest that patients (especially men) with a high VFA-to-abdominal fat ratio have a high risk of death. Thus, more attention should be paid to such patients.

Proteomic analysis reveals semaglutide impacts lipogenic protein expression in epididymal adipose tissue of obese mice.

Obesity is a global health problem with few pharmacologic options. Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue that induces weight loss. Yet, the role of semaglutide in adipose tissue has not yet been examined. The following study investigated the mechanism of semaglutide on lipid metabolism by analyzing proteomics of epididymal white adipose tissue (eWAT) in obese mice. A total of 36 C57BL/6JC mice were randomly divided into a normal-chow diet group (NCD, n = 12), high-fat diet (HFD, n = 12), and HFD+semaglutide group (Sema, n = 12). Mice in the Sema group were intraperitoneally administered semaglutide, and the HFD group and the NCD group were intraperitoneally administered an equal volume of normal saline. Serum samples were collected to detect fasting blood glucose and blood lipids. The Intraperitoneal glucose tolerance test (IPGTT) was used to measure the blood glucose value at each time point and calculate the area under the glucose curve. Tandem Mass Tag (TMT) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to study the expression of eWAT, while cellular processes, biological processes, corresponding molecular functions, and related network molecular mechanisms were analyzed by bioinformatics. Compared with the model group, the semaglutide-treated mice presented 640 differentially expressed proteins (DEPs), including 292 up-regulated and 348 down-regulated proteins. Bioinformatics analysis showed a reduction of CD36, FABP5, ACSL, ACOX3, PLIN2, ANGPTL4, LPL, MGLL, AQP7, and PDK4 involved in the lipid metabolism in the Sema group accompanied by a decrease in visceral fat accumulation, blood lipids, and improvement in glucose intolerance. Semaglutide can effectively reduce visceral fat and blood lipids and improve glucose metabolism in obese mice. Semaglutide treatment might have beneficial effects on adipose tissues through the regulation of lipid uptake, lipid storage, and lipolysis in white adipose tissue.

Food additive glycerol monocaprylate modulated systemic inflammation and gut microbiota without stimulating metabolic dysfunction in high-fat diet fed mice

Recent findings imply that great consideration should be given to the potential health risks of food additives on gut microbiota. Glycerol monocaprylate (GMC) is a widely consumed food preservative and emulsifier. Our results indicated that GMC significantly ameliorated visceral fat accumulation and systemic inflammation in high-fat diet (HFD)-fed mice. Furthermore, GMC induced improvements on the composition and function of gut microbiota, resulting in increased beneficial gut bacteria (Bifidobacterium and Lactobacillus) and promoted production of short chain fatty acids. Notably, GMC-induced metabolic amelioration is closely related to the regulation in gut microbiota. Overall, our findings supported that unlike the emulsifiers previously reported to damage intestinal health, GMC performed the potential on attenuating HFD-induced metabolic disorders and gut microbiota dysbiosis, which also refined on the safety evaluation of GMC on gut microbiota. Our findings suggest that when evaluating the safety of food additives with regards to gut microbiota, it is important to take into account the specific characteristics of the additive in question, rather than simply relying on its classification.

Plasma free amino acid profiles are associated with serum high molecular weight adiponectin levels in Japanese medical check-up population without type 2 diabetes mellitus

To prevent the progression of type 2 diabetes mellitus (T2DM), early detection and intervention are important. Several studies have already shown that the serum adiponectin level could be useful for evaluating the future risk of T2DM. Recently, plasma free amino acid (PFAA) concentrations have also emerged as potential biomarkers that predict the future onset of T2DM. In this study, we aimed to further characterise PFAA profiles by elucidating the association with the serum high molecular weight (HMW) adiponectin level in this cross-sectional study. A total of 1000 Japanese subjects who underwent medical check-ups were enrolled, and their plasma concentrations of 21 amino acids and clinical parameters were measured. The subjects without T2DM were divided into quartiles (Q1-4) by serum HMW adiponectin level, and the association with between PFAA concentrations was analysed. Concentrations of glutamate, alanine, proline, tyrosine, histidine, methionine, lysine, branched-chain amino acids (BCAAs) and tryptophan varied significantly according to the adiponectin quartile. Furthermore, serum adiponectin levels showed significant inverse correlations with these amino acids. The change in the PFAA profile in the group with the lowest adiponectin concentrations (Q1) was similar to that of T2DM patients. Although both adiponectin levels and PFAA concentrations are known to be altered by the accumulation of visceral fat and insulin resistance, the levels of glutamate, BCAA, lysine and tryptophan remain significantly associated with adiponectin level after adjustment for age, body mass index and homeostasis model assessment of insulin resistance, showing the direct association between PFAA concentrations and the serum HMW adiponectin level. Registration number: University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) UMIN000029920, registered on Nov 13th 2017 (prospectively registered).

Mechanisms of non-alcoholic fatty liver disease development in normal-weight individuals.

While non-alcoholic fatty liver disease (NAFLD) without inflammation or fibrosis is considered a relatively 'benign' disease, non-alcoholic steatohepatitis (NASH), by contrast, is characterized by marked inflammation in addition to lipid accumulation, and may include fibrosis, progression to cirrhosis and hepatocellular carcinoma. Obesity and type II diabetes are frequently associated with NAFLD/NASH; however, a significant number of lean individuals may develop these diseases. Little attention has been paid to the causes and mechanisms contributing to NAFLD development in normal-weight individuals. One of the main causes of NAFLD in normal-weight individuals is the accumulation of visceral and muscular fat and its interaction with the liver. Myosteatosis (triglyceride accumulation in the muscle) induces a loss of muscle by reducing blood flow and insulin diffusion, contributing to NAFLD. Normal-weight patients with NAFLD exhibit higher serum markers of liver damage and C-reactive protein levels, as well as more pronounced insulin resistance, compared to healthy controls. Notably, increased levels of C-reactive protein and insulin resistance are strongly correlated with the risk of developing NAFLD/NASH. Gut dysbiosis has also been associated with NAFLD/NASH progression in normal-weight individuals. More investigation is required to elucidate the mechanisms leading to NAFLD in normal-weight individuals.

A transdermal treatment with MC903 ameliorates diet-induced obesity by reducing visceral fat and increasing myofiber thickness and energy consumption in mice

AimMC903 is a synthetic derivative of vitamin D3 that has been designed to diminish its impact on calcium metabolism and is clinically used as a transdermal reagent for psoriasis. Animal studies showed that an oral or intraperitoneal vitamin D3 treatment prevented the development of obesity. In contrast, the bioavailability of orally administered vitamin D3 is reported to be low in obese patients. In the current study, we aimed to investigate the impact of a transdermal treatment with MC903 in established obese mice. We further studied the underlying mechanisms of MC903-mediated metabolic improvement.Materials and methodsMale C57BL/6 J mice were fed standard chow or a 60% high-fat diet (HFD) for 7 weeks, and a transdermal treatment with MC903 on the ear auricle was initiated thereafter. The metabolic profiles of mice were analyzed during 4 weeks of treatment, and mice were dissected for histological and gene expression analyses. The direct impacts of MC903 and vitamin D3 were investigated using 3T3-L1 adipocytes and C2C12 myotubes in vitro.ResultsHFD-fed mice showed significant increases in body and epididymal white adipose tissue (eWAT) weights with enlarged adipocytes. They exhibited glucose intolerance, decreased oxygen consumption, and chronic inflammation in eWAT. The transdermal treatment with MC903 significantly ameliorated these metabolic abnormalities in HFD-fed mice without affecting food consumption. In accordance with enhanced energy metabolism, myofiber diameters and the expression of uncoupling protein 3 (UCP3) in the gastrocnemius and soleus muscle were significantly increased in MC903-treated HFD mice. In addition, vitamin D3 and MC903 both suppressed adipogenic differentiation and enhanced lipolysis in 3T3-L1 adipocytes, and increased UCP3 expression in cultured C2C12 myotubes. Furthermore, MC903 increased oxygen consumption and UCP3 knockdown significantly decreased them in C2C12 myotubes.ConclusionsA transdermal treatment with MC903 increased myofiber diameter and energy metabolism and decreased visceral fat accumulation, thereby improving obesity and glucose intolerance in mice.

Visceral fat and attribute-based medicine in chronic kidney disease.

Visceral adipose tissue plays a central role in obesity and metabolic syndrome and is an independent risk factor for both cardiovascular and metabolic disorders. Increased visceral adipose tissue promotes adipokine dysregulation and insulin resistance, leading to several health issues, including systemic inflammation, oxidative stress, and activation of the renin-angiotensin-aldosterone system. Moreover, an increase in adipose tissue directly and indirectly affects the kidneys by increasing renal sodium reabsorption, causing glomerular hyperfiltration and hypertrophy, which leads to increased proteinuria and kidney fibrosis/dysfunction. Although the interest in the adverse effects of obesity on renal diseases has grown exponentially in recent years, the relationship between obesity and renal prognosis remains controversial. This may be attributed to the long clinical course of obesity, numerous obesity-related metabolic complications, and patients' attributes. Multiple individual attributes influencing the pathophysiology of fat accumulation make it difficult to understand obesity. In such cases, it may be effective to elucidate the pathophysiology by conducting research tailored to individual attributes from the perspective of attribute-based medicine/personalized medicine. We consider the appropriate use of clinical indicators necessary, according to attributes such as chronic kidney disease stage, level of visceral adipose tissue accumulation, age, and sex. Selecting treatments and clinical indicators based on individual attributes will allow for advancements in the clinical management of patients with obesity and chronic kidney disease. In the clinical setting of obesity-related nephropathy, it is first necessary to accumulate attribute-based studies resulting from the accurate evaluation of visceral fat accumulation to establish evidence for promoting personalized medicine.

The Influence of Obesity and Sedentary Lifestyle on Testosterone Level and the Main Indicators of the Metabolic Status in Young Men

Background. It is considered an established fact that there is an adverse trend in the male reproductive potential, which has been observed in various countries over the past decades. It is assumed that it can be formed due to the influence of individual lifestyle factors, in particular, a decrease in the level of physical activity and excessive nutrition, leading to obesity. However, the effect of obesity combined with sedentary or physically active lifestyle on the reproductive hormone level and metabolic homeostasis has not been studied well.&#x0D; Aims the aim of the work was to study the effects of obesity combined with sedentary or active physical lifestyle on the level of reproductive hormones and the main indicators of metabolic status of young men.&#x0D; Methods. In young male volunteers (median age 23 years, n = 295) from the general population, anthropometry was performed, which included body height and weight, waist and hip circumference, and body mass index (BMI); and they were also asked to fill out a questionnaire containing questions about individual lifestyle. In addition, serum concentrations of follicle stimulating and luteinizing hormones, testosterone, estradiol, inhibin B and triglycerides, total cholesterol, high and low density lipoprotein cholesterol, glucose, uric acid were evaluated.&#x0D; Results. The most important lipid metabolism disorders observed in overweight and obesity included an increase in triglycerides, total cholesterol, low-density lipoprotein cholesterol and a decrease in high-density lipoprotein cholesterol. Overweight and obesity in men was accompanied by an increase in waist and hip circumference, a decrease in the serum level of testosterone and inhibin B reaching in obese men the testosterone values characteristic for hypogonadism. Sedentary obese men had the increased waist circumference, lower testosterone level (median 13.6 vs. 18.0 nmol/L), elevated glucose level (median 5.8 vs. 4.9 mmol/L) compared to physically active obese men or those who prefer sports or physical recreation.&#x0D; Conclusions. In men, obesity negatively affects the serum level of testosterone and glucose, increases the accumulation of visceral fat, but a physically active lifestyle and sports give significant advantages to obese men, as it contributes to an increase in testosterone levels and normalization of metabolic parameters.

Sex discrepancy in establishing mouse visceral obesity model induced by high-fat diet.

To establish a mouse visceral obesity model, and to investigate the effect of animal sex on this model. Thirty-two 4-week-old BALB/c mice were randomly divided into female control group, female high-fat group, male control group and male high-fat group with 8 mice in each group.The control groups were given ordinary diet, and the high-fat groups were given high-fat diet. After 12 weeks of feeding, body weight, visceral fat, fasting blood glucose, glucose tolerance, blood lipid and metabolism-related hormone levels were measured, and the composition of gut microbiota of mice was analyzed by 16S rRNA sequencing. The high fat diet resulted in a significant increase of body weight and visceral fat content in male mice; the pathological results showed significantly increased fat area, accumulation of liver fat droplets, increased total cholesterol, fasting blood glucose, oral glucose tolerance and serum insulin levels (all P<0.05), as well as significant insulin resistance (P<0.01). However, the above changes were not significant in female mice. Compared with the control groups, there was an increase in the relative abundance of obesity-related gut microbiota in the model groups (such as Blautia), and the microbiota structure changed significantly, while the changes were less obvious in female mice. A visceral obesity mouse model has been stably established by feeding high-fat diet in BALB/c male mice, showing visceral fat accumulation, metabolic dysfunction and gut microbiota changes; while female mice are not sensitive in this obesity model.

Novel loci for hyperglycemia identified by QTL mapping of longitudinal phenotypes and congenic analysis

We previously reported that four hyperglycemia loci are located on three chromosomes in the Nagoya-Shibata-Yasuda (NSY) mouse model, commonly used to study type 2 diabetes. However, we did not search for hyperglycemia loci across all chromosomes. In this study, we performed quantitative trait loci (QTLs) mapping of longitudinal phenotypes from crosses between NSY (hyperglycemic) and C3H (normoglycemic) mice. We identified four new QTLs for hyperglycemia, namely Nidd5nsy, Nidd6nsy, Nidd1c3h, and Nidd2c3h, on Chromosome 1, 4, 10, and 13, respectively. These QTLs were associated with hyperglycemia in young mice and had attenuated effects in older mice. Nidd5nsy and Nidd6nsy were hyperglycemic with NSY alleles, and Nidd1c3h and Nidd2c3h were hyperglycemic with C3H alleles. We further bred Nidd5nsy congenic mice and demonstrated that Nidd5nsy has a strong effect on hyperglycemia when young, accompanied by insulin resistance and visceral fat accumulation. These results showed that the effects of individual QTLs strengthened or weakened with age, and that the sum of the effects of QTLs captured the age-related deterioration of glucose tolerance in individuals. Our results support the importance of longitudinal phenotypes in the genetic analysis of polygenic traits and have implications for the genetic basis and pathogenesis of type 2 diabetes in humans.

Potential Role of Oxidative Stress in the Production of Volatile Organic Compounds in Obesity.

Obesity is associated with numerous health issues such as sleep disorders, asthma, hepatic dysfunction, cancer, renal dysfunction, diabetes, cardiovascular complications, and infertility. Previous research has shown that the distribution of excess body fat, rather than excess body weight, determines obesity-related risk factors. It is widely accepted that abdominal fat is a serious risk factor for illnesses associated with obesity and the accumulation of visceral fat promotes the release of pro-oxidants, pro-inflammatory, and reactive oxygen species (ROS). The metabolic process in the human body produces several volatile organic compounds (VOCs) via urine, saliva, breath, blood, skin secretions, milk, and feces. Several studies have shown that VOCs are released by the interaction of ROS with underlying cellular components leading to increased protein oxidation, lipid peroxidation, or DNA damage. These VOCs released via oxidative stress in obese individuals may serves as a biomarker for obesity-related metabolic alterations and disease. In this review, we focus on the relationship between oxidative stress and VOCs in obesity.

Association between visceral fat accumulation and decline in the estimated glomerular filtration rate based on cystatin C in the Japanese urban population: the KOBE study.

Although metabolic syndrome, including visceral fat accumulation, causes kidney and cardiovascular diseases, the impact of visceral fat accumulation on mild decreased renal function remains unclear. This study examines the association between visceral fat area (VFA) measured by bioimpedance methods and the estimated glomerular filtration rate based on serum cystatin C (eGFRcys) in the Japanese urban population. This community-based cross-sectional study enrolled 952 individuals (287 men, 665 women) who participated in the second follow-up survey of the Kobe Orthopedic and Biomedical Epidemiological (KOBE) study. We compared the multivariate-adjusted means of eGFRcys among VFA quartile groups by gender using the analysis of covariance. Models were adjusted for age, high blood pressure, hypercholesterolemia, glucose intolerance, smoking, and alcohol use, and further adjusted for body mass index (BMI). The highest VFA quartile group had lower eGFRcys than the lowest VFA quartile group after adjusted for cardiometabolic risk factors, except for BMI (93.1 [95% confidence interval (CI), 90.1-96.2] vs. 82.1 [95% CI, 79.1-85.0] in men and 95.8 [95% CI, 94.1-97.5] vs. 89.4 [95% CI, 87.8-90.9] in women). Moreover, further adjustment for BMI revealed a similar result in men (93.5 [95% CI, 89.8-97.2] vs. 81.6 [95% CI, 77.9-85.3]), while no significant association was found in women. This study suggests a significant association between increased VFA levels and lower eGFRcys levels independent of cardiometabolic risk factors, such as glucose intolerance and hypercholesterolemia in men and women, as well as independent of BMI in men.

Goishi tea leaf powder affects lower body weight and visceral fat accumulation during energy restriction in obese rats.

Goishi tea is a unique Japanese post-fermented tea produced in Kochi prefecture. The aim of this study was to investigate whether the supplementation of energy-restricted diet with Goishi tea leaves affects body weight, visceral fat accumulation, and fecal lipids in diet-induced obese rats. 18 male Wistar rats were fed a high-fat diet for 12 weeks. Subsequently, the diet-induced obese rats were fed a low-energy diet containing 1% (G1 group) or 3% (G3 group) of Goishi tea leaf powder, or without any tea extracts (C group) for 4 weeks. After 4 weeks, body weight and body fat ratio were significantly lower in the G3 group than in the C group. Plasma insulin levels were significantly higher in the C group than in the G1 and G3 groups, whereas plasma leptin levels were significantly lower in the G3 group than in the C group. In addition, the lipid absorption rate was significantly lower in the G3 group than in the C and G1 groups. In conclusion, the administration of Goishi tea leaves under dietary restrictions might contribute to body weight reduction and inhibition of lipid absorption, as a diet therapy to help prevent obesity and metabolic syndrome. J. Med. Invest. 70 : 60-65, February, 2023.