Obesity-induced Abnormalities Research Articles

Novel perspectives on the link between obesity and cancer risk: from mechanisms to clinical implications.

Existing epidemiologic and clinical studies have demonstrated that obesity is associated with the risk of a variety of cancers. In recent years, an increasing number of experimental and clinical studies have unraveled the complex relationship between obesity and cancer risk and the underlying mechanisms. Obesity-induced abnormalities in immunity and biochemical metabolism, including chronic inflammation, hormonal disorders, dysregulation of adipokines, and microbial dysbiosis, may be important contributors to cancer development and progression. These contributors play different roles in cancer development and progression at different sites. Lifestyle changes, weight loss medications, and bariatric surgery are key approaches for weight-centered, obesity-related cancer prevention. Treatment of obesity-related inflammation and hormonal or metabolic dysregulation with medications has also shown promise in preventing obesity-related cancers. In this review, we summarize the mechanisms through which obesity affects the risk of cancer at different sites and explore intervention strategies for the prevention of obesity-associated cancers, concluding with unresolved questions and future directions regarding the link between obesity and cancer. The aim is to provide valuable theoretical foundations and insights for the in-depth exploration of the complex relationship between obesity and cancer risk and its clinical applications.

Effects of Soluble and Insoluble Fibre on Glycolipid Metabolism and Gut Microbiota in High-Fat-Diet-Induced Obese Mice.

Dietary fibre can alleviate or reduce the risk of obesity and obesity-induced abnormalities in glycolipid metabolism. However, the effects of different types of dietary fibre or their combinations on obesity remain unclear. Here, we explored the effects of different ratios of inulin soluble dietary fibre (ISDF) and barley leaf insoluble dietary fibre (BLIDF) on the body weight, glycolipid metabolism and gut microbiota of obese mice. Seven experimental groups were treated with different combinations of soluble and insoluble fibre, comprising HFD (high-fat diet without dietary fibre), BLIDF, ISDF, I3S1DF (insoluble/soluble = 3:1), I2S2DF (insoluble/soluble = 1:1), I1S3DF (insoluble/soluble = 1:3) and MIX (inulin, BLIDF and matcha powder fibre; insoluble/soluble = 3.6:1) groups. Our results showed that the BLIDF, ISDF and MIX treatments decreased the body weight gain of the HFD mice significantly after eight-week interventions. All the fibre intervention groups except the MIX group displayed lower fasting blood glucose and glycosylated serum protein levels than the HFD group. BLIDF, ISDF, I3S1DF and I2S2DF improved the glucose tolerance of the mice. Moreover, none of the dietary fibre interventions affected the liver lipid metabolism, while I3S1DF and I1S3DF improved the abnormal serum lipid metabolism. BLIDF, ISDF, I3S1DF and I2S2DF reduced the serum IL-6 levels, and BLIDF and I1S3DF increased SOD activity significantly. Additionally, all the dietary fibre interventions decreased the Firmicutes to Bacteroidota (F/B) ratio and increased the abundance of beneficial gut microbes differently. In short, our results suggest that different ratios of soluble and insoluble dietary fibre have unique impacts on mice body weight, glycolipid metabolism, inflammation and gut microbiota. The ratio of soluble to insoluble dietary fibre intake should be considered for specific health goals in the future.

Lactobacillus plantarum CCFM1180 attenuates obesity induced by estrogen deficiency by activating estrogen receptor alpha in abdominal adipose tissue and regulating gut microbiota-derived metabolitesestrogen

Lipid metabolism disorders commonly occur during menopause. Estrogen deficiency has been shown to lead to excessive energy intake and abnormal lipid metabolism in ovariectomized rats, resulting in obesity. Probiotics exhibit anti-obesity properties, and their underlying mechanism has been widely reported. In this study, we demonstrated the metabolic benefits of Lactobacillus plantarum CCFM1180 in suppressing appetite, controlling body weight, correcting obesity-induced abnormalities, enhancing liver lipid metabolism, and protecting liver function in estrogen-deficient rats. The mechanisms associated with the anti-obesity and anti-dyslipidemia effects of CCFM1180 on estrogen-deficient rats were clarified. The results showed that CCFM1180 dramatically reduced food intake by activating the expression of estrogen receptor alpha (ERα) and increasing the level of leptin in abdominal adipose tissue. These changes, combined with the increased butyrate concentration and recovered bile acid structure, helped enhance lipid metabolism. Additionally, CCFM1180 treatment was found to be safer than exogenous estrogen supplementation. Thus, L. plantarum CCFM1180 could be considered a new therapeutic strategy for preventing and alleviating menopausal lipid abnormalities.

Small RNA perspective of physical exercise-related improvement of male reproductive dysfunction due to obesity.

To study whether physical exercise can effectively ameliorate obesity-induced abnormalities in male fertility and provide a new perspective on the role of small noncoding RNAs in spermatogenesis in obese male mice. In this study, four-week-old C57/Bl6 male mice were randomly allocated to receive a control diet, a high-fat diet or physical exercise intervention for 40 weeks. Purified round spermatids and spermatozoa were obtained after intervention. Sperm motility, concentration, the ability of the sperm to undergo capacitation and acrosome reaction were assessed. Small RNA sequencing was conducted on round spermatids and spermatozoa. The small noncoding RNAs expression pattern was systematically analyzed. The spermatozoa concentration and percentage of motile spermatozoa, the capacitation and acrosome reaction, and the reproductive success rate, including mating success and pregnancy success, were decreased or delayed in the obesity group compared with controls. Physical exercise was able to restore the parameters to normal levels. Three microRNAs were consistently upregulated and 5 were downregulated in round spermatids and epididymal spermatozoa between the obesity and control groups. This report provides evidence that the adverse effects of obesity could be offset after physical exercise. small noncoding RNAs, especially microRNAs in germ cells, may play an important role in the effects of obesity and physical exercise on spermatozoa.

Body Mass Index and Body Fat Percentage for the Assessment of Obesity-Induced Abnormalities in Dynamic Lung Volumes

The body mass index (BMI) is commonly used in the assessment of obesity and overweight; however, its use in the diagnosis of adverse effects of obesity is questioned. This study aims to explore the agreement between the BMI and the calculated body fat percentage (BF%) in detecting obesity-induced ventilatory abnormalities. We carried out a cross-sectional study on a random sample of 150 healthy male students, aged 17 to 25, with a mean age of 20.8 ± 2.6 years. We measured the BMI, BF%, and pulmonary function of each participant. The students were classified into overweight-obese and normal groups based on the BMI and the BF% results. The Chi-square test was performed to analyze differences between the groups. About one-fifth of all participants had a fat mass ≥ 20%, among which 90% fulfilled the BMI definition of overweight and obesity (p < 0.05). The comparison between the two BF% groups showed that 20% of the overweight-obese group had a significant reduction in FEV1 (p= 0.025, Relative Risk= 3.00, 95% Confidence Interval= 1.13-7.99), and 23% of them had a significant reduction in FVC (p= 0.012, Relative Risk= 3.11, 95% Confidence Interval= 1.26-7.68). The changes in FEV1/FVC were statistically insignificant. The effects of the BMI categories on the dynamic lung volumes were statistically insignificant. The direct estimation of BF% is better than the calculation of BMI in the diagnosis of obesity-induced abnormalities in lung function. The use of BMI as an indicator of obesity in population health studies should be avoided.

Association between Lysosomal Dysfunction and Obesity-Related Pathology: A Key Knowledge to Prevent Metabolic Syndrome.

Obesity causes various health problems, such as type 2 diabetes, non-alcoholic fatty liver disease, and cardio- and cerebrovascular diseases. Metabolic organs, particularly white adipose tissue (WAT) and liver, are deeply involved in obesity. WAT contains many adipocytes with energy storage capacity and secretes adipokines depending on the obesity state, while liver plays pivotal roles in glucose and lipid metabolism. This review outlines and underscores the relationship between obesity and lysosomal functions, including lysosome biogenesis, maturation and activity of lysosomal proteases in WAT and liver. It has been revealed that obesity-induced abnormalities of lysosomal proteases contribute to inflammation and cellular senescence in adipocytes. Previous reports have demonstrated obesity-induced ectopic lipid accumulation in liver is associated with abnormality of lysosomal proteases as well as other lysosomal enzymes. These studies demonstrate that lysosomal dysfunction in WAT and liver underlies part of the obesity-related pathology, raising the possibility that strategies to modulate lysosomal function may be effective in preventing or treating the metabolic syndrome.

Effects of obesity and exercise on testicular leptin signal transduction and testosterone biosynthesis in male mice.

To explore the role of the testicular leptin and JAK-STAT[leptin (LEP)-JAK-STAT] pathway in testosterone biosynthesis during juvenile stages and exercise for weight loss, male C57BL/6J mice were randomly divided into normal-diet and high-fat diet groups. After 10 wk, mice in the high-fat diet-fed group were further divided randomly into obese control, obese moderate-volume exercise, and obese high-volume exercise groups. Mice in the obese moderate-volume exercise group were provided with 2 h/day, 6 days/wk swimming exercise for 8 wk, and mice in the obese high-volume exercise group underwent twice the amount of daily exercise intervention as the obese moderate-volume exercise group. The results showed that a high-fat diet causes obesity, leptin resistance, inhibition of the testicular LEP-JAK-STAT pathway, decreased mRNA and protein expression of steroidogenic factor-1, steroidogenic acute regulatory protein, and the P-450 side-chain cleavage enzyme, a decrease in the serum testosterone-to-estradiol ratio, and declines in sperm quality parameters. Both moderate and high-volume exercise were able to reduce body fat and increase the mRNA and protein expression of LEP-JAK-STAT, but only moderate exercise significantly increased the mRNA and protein expression of steroidogenic factor-1, steroidogenic acute regulatory protein, and P-450 side-chain cleavage enzyme and significantly reversed the serum testosterone-to-estradiol ratio and sperm quality parameters. These findings suggest that by impairing the testicular LEP-JAK-STAT pathway, early-stage obesity inhibits the biosynthesis of testosterone and sexual development and reduces male reproductive potential. Long-term moderate and high-volume exercise can effectively reduce body fat and improve obesity-induced abnormalities in testicular leptin signal transduction, whereas only moderate-volume exercise can reverse the negative impacts of obesity on male reproductive function.

Protective effect of resveratrol on spermatozoa function in male infertility induced by excess weight and obesity.

Male infertility is a complex, multifactorial and polygenic disease that contributes to ~50% cases of infertility. Previous studies have demonstrated that excess weight and obesity factors serve an important role in the development of male infertility. An increasing number of studies have reported that resveratrol may regulate the response of cells to specific stimuli that induce cell injury, as well as decrease germ cell apoptosis in mice or rats. In the present study, the semen quality and serum sex hormone levels were evaluated in 324 men, which included 73 underweight, 82 normal weight, 95 overweight and 74 obese men. All patients were referred to The Reproductive Medicine Center of Shanxi Women and Infants Hospital (Taiyuan, China) between January 2013 and January 2015. The aim of the present study was to investigate the effects of resveratrol treatment on the motility, plasma zinc concentration and acrosin activity of sperm from obese males. The sperm concentration, normal sperm morphology, semen volumes, DNA fragmentation rates and testosterone levels in men from the overweight and obese groups were markedly decreased when compared with men in the normal weight group. In addition, the progressive motility, seminal plasma zinc concentration and spermatozoa acrosin activity were notably decreased in the obese group compared with the normal weight group. However, estradiol levels were significantly increased in the overweight, obese and underweight groups compared with the normal weight group. Notably, semen samples from obese males with astenospermia treated with 0–100 µmol/l resveratrol for 30 min demonstrated varying degrees of improvement in sperm motility. When these semen samples were treated with 30 µmol/l resveratrol, sperm motility improved when compared to other doses of resveratrol. Therefore, 30 µmol/l resveratrol was selected for further experiments. Upon treatment of semen samples with resveratrol (30 µmol/l) for 30 min, the seminal plasma zinc concentration and spermatozoa acrosin activity increased significantly in the experimental group compared with the control group. These data suggest that male obesity negatively impacts on male reproductive potential, not only through altering hormone levels, but also by directly altering sperm function. In addition, resveratrol may have a therapeutic and protective effect against obesity-induced abnormalities in semen.

Assessment of neuroinflammation in a mouse model of obesity and β-amyloidosis using PET.

BackgroundObesity has been identified as a risk factor for cognitive decline and Alzheimer’s disease (AD). The aim of this study was to investigate the effect of obesity on neuroinflammation and cerebral glucose metabolism using PET in a mouse model of β-amyloidosis and determine the relationship between these PET imaging biomarkers, pathogenic changes, and functional outcomes.MethodsThree-month-old C57BL/J6 mice were fed either a standard (control group) or high-fat diet (obese group) for 3 months and intracerebroventricularly infused with vehicle or human beta amyloid 1-42 (Aβ42). We assessed obesity-induced abnormalities in peripheral metabolic indices including adiposity, fasting glucose, and glucose tolerance. Brain glucose metabolism was assessed by 18F-FDG PET, and glial activation was assessed using the translocator protein (TSPO) ligand 11C-PBR-28. TSPO expression was confirmed by immunohistochemistry of brain sections obtained from scanned mice. The association between inflammatory state and 11C-PBR-28 PET signals was characterized by examination of the cytokine expression profile in both the serum and hippocampus by antibody array. Learning and memory performance was assessed in the object recognition task, and anxiety-related behavior was assessed in the elevated plus maze.ResultsObesity combined with Aβ infusion promoted neuroinflammation and cerebral hypermetabolism, and these signals were significant predictors of learning and memory performance in the object recognition task. In vivo TSPO signals were associated with inflammatory markers including CXCL1, CXCL2, CXCL12, CCL3, CCL5, TIMP-1, G-CSF, sICAM-1, and IL-1ra.ConclusionsIn vivo cerebral metabolism and TSPO signals indicate that obesity can accelerate amyloid-induced inflammation and associated cognitive decline.

The Role of Obesity in Cardiomyopathy and Nephropathy

The growing incidence of obesity and related complications such as cardiomyopathy and nephropathy remains a global health challenge. Many pathophysiological factors including inflammation, oxidative stress and endothelial dysfunction are implicated in obesity- induced abnormalities in the heart and kidney. Moreover, obesity and nutrient-overload are associated with the activation of different inflammatory/oxidative signaling pathways such as endoplasmic reticulum stress, nuclear factor-kappaB (NF-κB), toll-like-receptor-4 (TLR4) and the renin-angiotensin-aldosterone system (RAAS). The pathophysiological role of RAAS, TLR4 and NF-κB in perturbing physiological milieu is well acknowledged. Several pharmacological agents have been formulated to target one or more of these pathways. Although significant strides have been made in elucidating mechanisms implicated in obesity-related cardio-renal diseases, much still has to be done. The pathophysiology of cardiomyopathy and nephropathy is complex and multifaceted. Besides NF-κ B, TLR4, RAAS and inflammatory mediators such as cytokines and chemokines, a wide spectrum of different factors including, the environment, diets, lifestyles, genetics and epigenetics are also involved. With such multifactorial etiology, it remains a daunting challenge to identify the factor(s) that initiate the activation and propagation of adverse stimuli that eventually lead to cardiomyopathy and/or nephropathy in obese individuals. Similarly, the mechanisms of such activation and propagation should be clearly elucidated. Should these hurdles be overcome, there would be a greater likelihood for the development of more-effective therapeutic strategies for the prevention, treatment and management of obesity-induced cardiomyopathy and nephropathy. The present review examines the role of inflammation, oxidative stress and endothelial dysfunction in obesity-induced abnormalities in heart and kidney.

Role of Cardiovascular Ultrasound in the Evaluation of Obese Subjects.

Obesity represents a worldwide increasing health problem. Obesity, through complex and not fully understood pathogenetic mechanisms, induces different structural and functional changes of left heart chambers, right heart chambers, and arteries. Ultrasound techniques are the first choice for a comprehensive assessment of the cardiovascular adaptation to obesity. This review summarizes the up-to-date literature on the topic, with particular focus on the main clinical studies, which range over different cardiovascular adaptations to obesity, namely left ventricular mass, diastolic function, right ventricle structure and function, arterial stiffness, and intima-media thickness. Also, the importance of epicardial fat and of the degree of obesity is described. Finally, the role of weight loss and bariatric surgery and the study of cardiovascular obesity-induced abnormalities in children and adolescent are discussed.

Bixin Activates PPARα and Improves Obesity-Induced Abnormalities of Carbohydrate and Lipid Metabolism in Mice

Peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that regulates the expression of the genes involved in fatty acid oxidation. PPARα activators induce fatty acid oxidation in the liver, thereby improving lipid and carbohydrate metabolism in obese mice. In this study, the dietary cis-carotenoids bixin and norbixin, which are commonly used in the food coloring industry, were found to activate PPARα by luciferase reporter assays using GAL4/PPARα chimeric and full-length PPARα systems. Treatment with bixin and norbixin induced the mRNA expression of PPARα target genes involved in fatty acid oxidation in PPARα-expressing HepG2 hepatocytes. In obese KK-Ay mice, bixin treatment suppressed the development of hyperlipidemia and hepatic lipid accumulation. In the livers of bixin-treated mice, the mRNA levels of PPARα target genes related to fatty acid oxidation were up-regulated. Moreover, bixin treatment also improved obesity-induced dysfunctions of carbohydrate metabolism, such as hyperglycemia, hyperinsulinemia, and hypoadiponectinemia. Glucose tolerance test and insulin tolerance test revealed that glucose intolerance and insulin resistance in KK-Ay obese mice were attenuated by the treatment with bixin. These results indicate that bixin acts as a food-derived agonist of PPARα, and bixin treatment is useful for the management of obesity-induced metabolic dysfunctions in mice.