Cigarette smoking blocks the benefit from reduced weight gain for insulin action by shifting lipids deposition to muscle.

Cigarette smoking (CS) is known to reduce body weight and this often masks its real effect on insulin action. The present study tested the hypothesis that CS can divert lipid deposition to muscles to offset the supposed benefit of reduced body weight gain on insulin signalling in this major site for glucose tolerance (or insulin action). The study was conducted in mice exposed to chronic CS followed by either a chow (CH) diet or a high-fat (HF) diet. CS increased triglyceride (TG) levels in both plasma and muscle despite a reduced body weight gain and adiposity. CS led to glucose intolerance in CH-fed mice and they retained the glucose intolerance that was induced by the HF diet. In adipose tissue, CS increased macrophage infiltration and the mRNA expression of TNFα but suppressed the protein expression of adipose triglyceride lipase and PPARγ. While CS increased hormone-sensitive lipase and suppressed the mRNA expression of leptin, these effects were blunted in HF-fed mice. These results imply that CS impairs insulin signalling in skeletal muscle via accumulated intramuscular lipids from lipolysis and lipodystrophy of adipose tissues. This may explain why smokers may not benefit from insulin sensitising effects of reduced body weight gain.

Altered Regulation of adipomiR Editing with Aging.

Adipose dysfunction with aging increases risk to insulin resistance and other chronic metabolic diseases. We previously showed functional changes in microRNAs involved in pre-adipocyte differentiation with aging resulting in adipose dysfunction. However, the mechanisms leading to this dysfunction in microRNAs in adipose tissue (adipomiRs) during aging are not well understood. We determined the longitudinal changes in expression of adipomiRs and studied their regulatory mechanisms, such as miRNA biogenesis and editing, in an aging rodent model, with Fischer344 × Brown-Norway hybrid rats at ages ranging from 3 to 30 months (male/females, n > 8). Expression of adipomiRs and their edited forms were determined by small-RNA sequencing. RT-qPCR was used to measure the mRNA expression of biogenesis and editing enzymes. Sanger sequencing was used to validate editing with aging. Differential expression of adipomiRs involved in adipocyte differentiation and insulin signaling was altered with aging. Sex- and age-specific changes in edited adipomiRs were observed. An increase in miRNA biogenesis and editing enzymes (ADARs and their splice variants) were observed with increasing age, more so in female than male rats. The adipose dysfunction observed with age is attributed to differences in editing of adipomiRs, suggesting a novel regulatory pathway in aging.

Famine exposure in early life is associated with visceral adipose dysfunction in adult females.

PURPOSE: Epidemiologic studies have revealed that early life malnutrition increases later risk of metabolic diseases. The visceral adiposity index (VAI) is a novel sex-specific index that shows promise as a marker of visceral adipose dysfunction. We aimed to explore whether exposure to the Chinese famine between 1959 and 1962 during fetal and childhood periods was related to VAI in adulthood. METHODS: Our data source was SPECT-China, a population-based cross-sectional study in East China. Overall, 5295 subjects from 16 sites were divided into fetal-exposed (1959-1962), childhood-exposed (1949-1958), adolescence/young adult-exposed (1921-1948), and non-exposed (1963-1974) groups. The associations of life periods when exposed to famine with VAI were assessed via linear regression. RESULTS: Compared with the non-exposed women (1963-1974), the fetal- and the childhood-exposed women had significantly greater VAI values (P < 0.05), but this difference was not observed in men. In the fetal- and childhood-exposed women, there was a significant positive association of famine exposure with VAI after adjusting for age, current smoking, rural/urban residence, and economic status (both P < 0.05). Further adjustments for diabetes and hypertension did not attenuate this association (both P < 0.05). However, such association was not observed in men. CONCLUSIONS: Exposure to famine in early life may have a significant association with visceral adipose dysfunction in adult females. The fetal age and childhood may be important time windows for nutrition relief to prevent visceral adipose dysfunction.

Protein kinase C-beta: An emerging connection between nutrient excess and obesity.

There is currently a global epidemic of obesity as a result of recent changes in lifestyle. Excess body fat deposition is caused by an imbalance between energy intake and energy expenditure due to interactions between genetic and environmental factors. The signals and biological mechanisms that trigger fat accumulation by disrupting energy homeostasis are not well understood. There is considerable evidence now supporting a possible role of protein kinase C beta (PKCß) in energy homeostasis. This review highlights recent findings on the role of PKCß activation in the genesis and progression of obesity, and of PKCß repression in mediating the beneficial effects of physical exercise. Available data support a model in which adipose PKCß activation is among the initiating events that disrupt mitochondrial function through interaction with p66shc and amplify fat accumulation and adipose dysfunction, with systemic consequences. Manipulation of PKCß levels, activity, or signaling could provide a therapeutic approach to combat obesity and associated metabolic disorders.

Adipose Dysfunction Indices as a Key to Cardiometabolic Risk Assessment-A Population-Based Study of Post-Myocardial Infarction Patients.

Anthropometric indices, such as the BMI (body mass index), WC (waist circumference), and WHR (waist-hip ratio) are commonly used for cardiometabolic risk assessment. Consequently, in the context of evaluating cardiometabolic risk in the post-MI population, it is worthwhile to consider indices such as the Visceral Adiposity Index (VAI) and Body Adiposity Index (BAI), which have emerged as valuable risk assessment tools in clinical trials. The aim of this study was to provide a more comprehensive understanding of the importance of anthropometric indices and body composition analysis in evaluating the cardiometabolic risk among post-myocardial infarction patients. In the pursuit of this objective, this study involved assessing the BMI, WC, WHR, WHtR, VAI, BAI, and body composition in a population of patients. This study enrolled a total of 120 patients hospitalised at the Silesian Centre for Heart Diseases (SCCS) due to MI, and body composition analysis evaluated various parameters including the percentage of adipose tissue (FatP) [%], total adipose tissue (FatM) [kg], fat-free mass (FFM) [kg], muscle mass (PMM) [kg], total body water (TBW) [kg], and visceral adipose tissue (VFAT). The mean BMI for the entire group was 27.76 ± 4.08, with women exhibiting a significantly lower value compared with men (26.66 ± 3.33 vs. 28.16 ± 4.27). The mean values obtained for the WHR, WHtR, BAI, and VAI were 0.97 ± 0.08, 0.59 ± 0.07, 28.37 ± 5.03, and 3.08 ± 3.50, respectively. Based on the visceral adiposity index (VAI), in 47.5% patients, there was no adipose tissue dysfunction, with a higher proportion among women (71.88%) compared with men (38.64%). What raises concern is that 32.50% of patients had acute ATD, with a significantly higher prevalence among men (38.64%) compared with women (15.63%). Conclusion: The study results suggest that the BMI, WC, and WHR have their limitations, whereas the WHtR, VAI, and BAI provide a more comprehensive view of cardiometabolic risk, especially in the context of adipose tissue distribution and its metabolic consequences. Incorporating the WHtR, VAI, and BAI into routine clinical practice may enhance the management of cardiometabolic risk, especially among post-MI patients.

Blood Lead Level Is Associated with Visceral Adipose Dysfunction in Patients with Type 2 Diabetes.

We aimed to explore whether an elevated blood lead level (BLL) is associated with visceral adipose dysfunction in patients with type 2 diabetes mellitus (T2DM). Four thousand one hundred and fourteen diabetic participants were enrolled from seven communities in Shanghai in 2018 in the cross-sectional METAL study. BLL was measured by graphite furnace atomic absorption spectrometry. Visceral adiposity index (VAI) and lipid accumulation product (LAP)were calculated by simple anthropometric and biochemical parameters. We found that medians (IQR) of BLL were 26.0 µg/L (18.0-37.0) for men and 25.0 µg/L (18.0-35.0) for women, respectively. In men, each doubling of BLL was associated with a 2.0% higher VAI (95% CI, 0.6 to 3.5%) and 1.8% higher LAP (95% CI, 0.2 to 3.3%) after full adjustment. Using the lowest BLL quartile as the referent group, significant positive trends were observed for BLL with VAI and LAP. In women, each doubling of BLL was associated with a 1.9% higher LAP (95% CI, 0.6 to 3.1%). Additionally, there was a marginally significant positive association between BLL and VAI, either using log2-transformed concentrations as continuous variables or categorized in quartiles. In conclusion, lead exposure is associated with visceral adipose dysfunction in patients with T2DM. Further prospective studies are warranted to confirm our findings.

Relative Handgrip Strength is Inversely Associated with Hypertension in Consideration of Visceral Adipose Dysfunction: A Nationwide Cross-Sectional Study in Korea.

This study investigated the associations of relative handgrip strength (rHGS) and hypertension. Individual differences in visceral adipose dysfunction (VAD) were evaluated to verify whether rHGS was associated with a reduction in the risk of hypertension, even in individuals with VAD. We included 77,991 participants (50,616 women) from nationwide cohorts in Korea. Participants were categorized into three groups based on sex-specific tertiles of rHGS (Low, Mid, and High). The visceral adiposity index (VAI) was used to evaluate VAD. The multiple logistic regression model was used to assess the risk of hypertension. High rHGS is associated with reduction of hypertension risk in 38 and 26% of men and women, respectively, although rHGS was significantly low in women compared to men. The benefit of rHGS was observed from middle-aged to older participants in both sexes. High rHGS is associated with risk reduction for hypertension in both VAD and non-VAD groups. In the VAD group, compared to Low rHGS, High rHGS was associated with 32 and 22% risk reductions in hypertension in men and women, respectively, and these associations remained significant even when classified according to age, such as in middle-aged and older subgroups. Therefore, the present study suggests that high levels of rHGS are significantly associated with a reduced risk of hypertension even in participants with VAD. Thus, maintaining a higher level of rHGS may be associated with protective benefits against hypertension.

Recent Advances in Adipose Tissue Dysfunction and Its Role in the Pathogenesis of Non-Alcoholic Fatty Liver Disease.

Obesity is a serious ongoing health problem that significantly increases the incidence of nonalcoholic fatty liver disease (NAFLD). During obesity, adipose tissue dysfunction is obvious and characterized by increased fat deposition (adiposity) and chronic low-grade inflammation. The latter has been implicated to critically promote the development and progression of NAFLD, whose advanced form non-alcoholic steatohepatitis (NASH) is considered one of the most common causes of terminal liver diseases. This review summarizes the current knowledge on obesity-related adipose dysfunction and its roles in the pathogenesis of hepatic steatosis and inflammation, as well as liver fibrosis. A better understanding of the crosstalk between adipose tissue and liver under obesity is essential for the development of new and improved preventive and/or therapeutic approaches for managing NAFLD.

Adipose Morphology: a Critical Factor in Regulation of Human Metabolic Diseases and Adipose Tissue Dysfunction.

Emerging evidence highlights that dysfunction of adipose tissue contributes to impaired insulin sensitivity and systemic metabolic deterioration in obese state. Of note, adipocyte hypertrophy serves as a critical event which associates closely with adipose dysfunction. An increase in cell size exacerbates hypoxia and inflammation as well as excessive collagen deposition, finally leading to metabolic dysregulation. Specific mechanisms of adipocyte hypertrophy include dysregulated differentiation and maturation of preadipocytes, enlargement of lipid droplets, and abnormal adipocyte osmolarity sensors. Also, weight loss therapies exert profound influence on adipocyte size. Here, we summarize the critical role of adipocyte hypertrophy in the development of metabolic disturbances. Future studies are required to establish a standard criterion of size measurement to better clarify the impact of adipocyte hypertrophy on changes in metabolic homeostasis.

Chronic inflammation, cardiometabolic diseases and effects of treatment: Psoriasis as a human model.

Chronic inflammation in humans is associated with accelerated development of cardiometabolic diseases such as myocardial infarction, stroke, and diabetes. Strong evidence from animal models and human interventional trials including CANTOS (The Canakinumab Anti-inflammatory Thrombosis Outcome Study) suggests that targeting residual systemic inflammation in humans may impart a benefit in reducing cardiometabolic diseases. Diseases associated with heightened immune-activation and systemic inflammation including psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and human immunodeficiency virus infection are associated with upwards of two to seven-fold risk of future adverse cardiac events even when adjusted for traditional risk factors. Over the past decade, psoriasis has been utilized as a human model to study inflammatory-induced cardiometabolic dysfunction and to better understand residual risk due to inflammation. The high prevalence and early onset of cardiovascular disease in psoriasis enhances the likelihood of discovering novel pathways in vascular disease progression when followed over time. Furthermore, the United States Food and Drug Administration approved treatments for psoriasis include cytokine inhibitors (anti-tumor necrosis factor, anti-interleukin 17, anti-interleukin 12/23) which while treating the skin disease provide a unique opportunity to characterize how treating the inflammatory pathways may impact atherosclerosis. Herein, we provide a review of chronic inflammation, cardiometabolic disease associations, and treatment effects with a focus on psoriasis as a human model of study.

Sexual dimorphism in obesity-related genes in the epicardial fat during aging.

Aging increases the risk of cardiovascular disease and metabolic syndrome. Alterations in epicardial fat play an important pathophysiological role in coronary artery disease and hypertension. We investigated the impact of normal aging on obesity-related genes in epicardial fat. Sex-specific changes in obesity-related genes with aging in epicardial fat (EF) were determined in young (6 months) and old (30/36 months) female and male, Fischer 344 × Brown Norway hybrid (FBN) rats, using a rat obesity RT2 PCR Array. Circulating sex hormone levels, body and heart weights were determined. Statistical significance was determined using two-tailed Student's t test and Pearson's correlation. Our results revealed sex-specific differences in obesity-related genes with aging. Dramatic changes in the expression profile of obesity-related genes in EF with aging in female, but not in male, FBN rats were observed. The older (30 months) female rats had more significant variations in the abundance of obesity-related genes in the EF compared to that seen in younger female rats or both age groups in male rats. A correlation of changes in obesity-related genes in EF to heart weights was observed in female rats, but not in male rats with aging. No correlation was observed to circulating sex hormone levels. Our findings indicate a dysfunctional EF in female rats with aging compared to male rats. These findings, with further functional validation, might help explain the sex differences in cardiovascular risk and mortality associated with aging observed in humans.