Role of microbiota-derived lipopolysaccharide in adipose tissue inflammation, adipocyte size and pyroptosis during obesity.

It has been established that ingestion of a high-fat diet increases the blood levels of lipopolysaccharides (LPS) from Gram-negative bacteria in the gut. Obesity is characterised by low-grade systemic and adipose tissue inflammation. This is suggested to be implicated in the metabolic syndrome and obesity. In the present review, we hypothesise that LPS directly and indirectly participates in the inflammatory reaction in adipose tissue during obesity. The experimental evidence shows that LPS is involved in the transition of macrophages from the M2 to the M1 phenotype. In addition, LPS inside adipocytes may activate caspase-4/5/11. This may induce a highly inflammatory type of programmed cell death (i.e. pyroptosis), which also occurs after infection with intracellular pathogens. Lipoproteins with or without LPS are taken up by adipocytes. Large adipocytes are more metabolically active and potentially more exposed to LPS than small adipocytes are. Thus, LPS might be involved in defining the adipocyte death size and the formation of crown-like structures. The adipocyte death size is reached when the intracellular concentration of LPS initiates pyroptosis. The mechanistic details remain to be elucidated, but the observations indicate that adipocytes are stimulated to cell death by processes that involve LPS from the gut microbiota. There is a complex interplay between the composition of the diet and microbiota. This influences the amount of LPS that is translocated from the gut. In particular, the lipid content of a meal may correlate with the amount of LPS built in to chylomicrons.

Current and future strategies for the nutritional management of cardiometabolic complications of androgen deprivation therapy for prostate cancer.

Androgen deprivation therapy (ADT) is used widely as part of a combined modality for the treatment of prostate cancer. However, ADT has also been associated with the development of cardiometabolic complications that can increase mortality from cardiovascular events. There is emerging evidence to suggest that ADT-related cardiometabolic risk can be mitigated by diet and lifestyle modification. While the clinical focus for a nutritional approach for achieving this effect is unclear, it may depend upon the timely assessment and targeting of dietary changes to the specific risk phenotype of the patient. The present review aims to address the metabolic origins of ADT-related cardiometabolic risk, existing evidence for the effects of dietary intervention in modifying this risk, and the priorities for future dietary strategies.

Association of food consumption with total volumes of visceral and subcutaneous abdominal adipose tissue in a Northern German population.

Excess accumulation of visceral adipose tissue (VAT) is a known risk factor for cardiometabolic diseases; further, subcutaneous abdominal adipose tissue (SAAT) and the ratio of both (VAT:SAAT ratio) have been discussed as potentially detrimental. Information about the association between diet and adipose tissue is scarce. This study aimed to identify food group intake associated with VAT and SAAT and the VAT:SAAT ratio in a Northern German population. A cross-sectional analysis was conducted in 344 men and 241 women who underwent an MRI to quantify total volumes of VAT and SAAT. Intake of fourteen food groups was assessed with a self-administered 112-item FFQ. Linear regression models adjusted for age, sex, energy intake, physical activity, intake of other food groups and mutual adjustment for VAT and SAAT were calculated to analyse the associations between standardised food group intake and VAT and SAAT, or the VAT:SAAT ratio. Intakes of potatoes (P=0·043) and cakes (P=0·003) were positively and inversely, respectively, associated with both VAT and SAAT. By contrast, intake of cereals was negatively associated with VAT (P=0·045) only, whereas intakes of eggs (P=0·006) and non-alcoholic beverages (P=0·042) were positively associated with SAAT only. The association between eggs and non-alcoholic beverages with SAAT remained significant after further consideration of VAT. Intake of non-alcoholic beverages was also inversely associated with the VAT:SAAT ratio (P=0·001). Our analysis adds to the evidence that intake of foods is independently associated with VAT or SAAT volumes.

Vitamin D receptor Cdx-2-dependent response of central obesity to vitamin D intake in the subjects with type 2 diabetes: a randomised clinical trial.

This study aimed to investigate the effects of daily intake of vitamin D-fortified yogurt drink (doogh) on central obesity indicators in subjects with type 2 diabetes (T2D) and the possible modulation of this effect by vitamin D receptor (VDR) Cdx-2 genotypes. A total of sixty T2D subjects were randomly allocated to two groups to receive either plain doogh (PD; n 29, containing 170 mg Ca and no vitamin D/250 ml) or vitamin D3-fortified doogh (FD; n 31, containing 170 mg Ca and 12·5 µg/250 ml) twice a day for 12 weeks. 25-hydroxyvitamin D (25(OH)D), glycaemic as well as adiposity indicators were evaluated before and after the intervention. VDR-Cdx-2 genotypes in extended number of T2D subjects in the FD group (n 60) were determined as AA, GA and GG. After 12 weeks, in FD compared with PD, serum 25(OH)D increased (+35·4 v. -4·8 nmol/l; P<0·001) and mean changes of waist circumference (WC; -1·3 v. +1·6 cm; P=0·02), body fat mass (FM; -1·9 v. +0·60 %; P=0·008), truncal fat (TF; -1·1 v. 0·13 %; P=0·003) and visceral adipose tissue (-0·80 v. +0·37 AU; P<0·001) decreased significantly. Circulating 25(OH)D was raised only in the AA group (34·8 nmo/l in AA group v. -6·4 nmol/l in AG and -1·6 nmol/l in GG groups; P<0·001), which was accompanied by a significant decrease in changes of WC (P=0·004), FM% (P=0·01) and TF% (P<0·001) in the AA genotype. Daily intake of vitamin D-FD for 12 weeks improved the central obesity indices in T2D subjects, and the improvement was more pronounced in the carriers of the AA genotype of VDR-Cdx-2.

Factors associated with poor sleep quality in midlife Singaporean women: The Integrated Women's Health program (IWHP).

Objective: To examine factors associated with poor sleep quality in community-dwelling midlife women. Methods: Healthy women (aged 45-69 years) of Chinese, Malay and Indian ethnicities attending well-women clinics at the National University Hospital, Singapore, completed the Pittsburgh Sleep Quality Index (PSQI). A PQSI score >5 denoted poor sleep quality. The women filled out validated questionnaires covering menopausal and genito-urinary symptoms, and mental health. Physical performance was measured. Bone mineral density and visceral adiposity were assessed by dual energy X-ray absorptiometry. Binary logistic regression analyses assessed independent factors for poor sleep. Results: Poor sleep quality was reported in 38.2% of women (n = 1094, mean age: 56.4 ± 6.2 years). Indian women had higher sleep disturbance scores than Chinese women (mean ± SD: 1.33 ± 0.58 vs 1.17 ± 0.49). Malays experienced more daytime dysfunction (0.54 ± 0.60 vs 0.33 ± 0.55) and had a higher overall PSQI score (6.00 ± 3.31 vs 5.02 ± 2.97) than the Chinese. A low education level (aOR: 1.76, 95% CI: 1.01-3.05), feelings of irritability (2.67, 1.56-4.60) and vaginal dryness (1.62, 1.03-2.54) were associated with poor sleep quality in the adjusted multivariable model. Women with moderate to severe disability were ∼3 times (2.99, 1.20-7.44) more likely to experience less than ideal sleep quality, while urinary incontinence (1.53, 1.08-2.17) and breast cancer history (2.77, 1.36-5.64) were also associates of poor sleep quality. Conclusion: Self-reports of education level, irritability, vaginal dryness, disability, urinary incontinence, and breast cancer history were independently related to poor sleep. Ethnic differences suggest the need for targeted interventions among the ethnic groups.

CT-based radiomics signature of visceral adipose tissue for prediction of disease progression in patients with Crohn's disease: A multicentre cohort study.

Background: Visceral adipose tissue (VAT) is involved in the pathogenesis of Crohn's disease (CD). However, data describing its effects on CD progression remain scarce. We developed and validated a VAT-radiomics model (RM) using computed tomography (CT) images to predict disease progression in patients with CD and compared it with a subcutaneous adipose tissue (SAT)-RM. Methods: This retrospective study included 256 patients with CD (training, n = 156; test, n = 100) who underwent baseline CT examinations from June 19, 2015 to June 14, 2020 at three tertiary referral centres (The First Affiliated Hospital of Sun Yat-Sen University, The First Affiliated Hospital of Shantou University Medical College, and The First People's Hospital of Foshan City) in China. Disease progression referred to the development of penetrating or stricturing diseases or the requirement for CD-related surgeries during follow-up. A total of 1130 radiomics features were extracted from VAT on CT in the training cohort, and a machine-learning-based VAT-RM was developed to predict disease progression using selected reproducible features and validated in an external test cohort. Using the same modeling methodology, a SAT-RM was developed and compared with the VAT-RM. Findings: The VAT-RM exhibited satisfactory performance for predicting disease progression in total test cohort (the area under the ROC curve [AUC] = 0.850, 95% confidence Interval [CI] 0.764-0.913, P < 0.001) and in test cohorts 1 (AUC = 0.820, 95% CI 0.687-0.914, P < 0.001) and 2 (AUC = 0.871, 95% CI 0.744-0.949, P < 0.001). No significant differences in AUC were observed between test cohorts 1 and 2 (P = 0.673), suggesting considerable efficacy and robustness of the VAT-RM. In the total test cohort, the AUC of the VAT-RM for predicting disease progression was higher than that of SAT-RM (AUC = 0.786, 95% CI 0.692-0.861, P < 0.001). On multivariate Cox regression analysis, the VAT-RM (hazard ratio [HR] = 9.285, P = 0.005) was the most important independent predictor, followed by the SAT-RM (HR = 3.280, P = 0.060). Decision curve analysis further confirmed the better net benefit of the VAT-RM than the SAT-RM. Moreover, the SAT-RM failed to significantly improve predictive efficacy after it was added to the VAT-RM (integrated discrimination improvement = 0.031, P = 0.102). Interpretation: Our results suggest that VAT is an important determinant of disease progression in patients with CD. Our VAT-RM allows the accurate identification of high-risk patients prone to disease progression and offers notable advantages over SAT-RM. Funding: This study was supported by the National Natural Science Foundation of China, Guangdong Basic and Applied Basic Research Foundation, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Nature Science Foundation of Shenzhen, and Young S&T Talent Training Program of Guangdong Provincial Association for S&T. Translation: For the Chinese translation of the abstract see Supplementary Materials section.

Indian National Association for Study of the Liver (INASL) Guidance Paper on Nomenclature, Diagnosis and Treatment of Nonalcoholic Fatty Liver Disease (NAFLD).

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease globally and in India. The already high burden of NAFLD in India is expected to further increase in the future in parallel with the ongoing epidemics of obesity and type 2 diabetes mellitus. Given the high prevalence of NAFLD in the community, it is crucial to identify those at risk of progressive liver disease to streamline referral and guide proper management. Existing guidelines on NAFLD by various international societies fail to capture the entire landscape of NAFLD in India and are often difficult to incorporate in clinical practice due to fundamental differences in sociocultural aspects and health infrastructure available in India. A lot of progress has been made in the field of NAFLD in the 7 years since the initial position paper by the Indian National Association for the Study of Liver on NAFLD in 2015. Further, the ongoing debate on the nomenclature of NAFLD is creating undue confusion among clinical practitioners. The ensuing comprehensive review provides consensus-based, guidance statements on the nomenclature, diagnosis, and treatment of NAFLD that are practically implementable in the Indian setting.

Association of Cardiometabolic Disease With Cancer in the Community.

Background: Obesity and cardiometabolic dysfunction have been associated with cancer risk and severity. Underlying mechanisms remain unclear. Objectives: The aim of this study was to examine associations of obesity and related cardiometabolic traits with incident cancer. Methods: FHS (Framingham Heart Study) and PREVEND (Prevention of Renal and Vascular End-Stage Disease) study participants without prevalent cancer were studied, examining associations of obesity, body mass index (BMI), waist circumference, visceral adipose tissue (VAT) and subcutaneous adipose tissue depots, and C-reactive protein (CRP) with future cancer in Cox models. Results: Among 20,667 participants (mean age 50 years, 53% women), 2,619 cancer events were observed over a median follow-up duration of 15 years. Obesity was associated with increased risk for future gastrointestinal (HR: 1.30; 95% CI: 1.05-1.60), gynecologic (HR: 1.62; 95% CI: 1.08-2.45), and breast (HR: 1.32; 95% CI: 1.05-1.66) cancer and lower risk for lung cancer (HR: 0.62; 95% CI: 0.44-0.87). Similarly, waist circumference was associated with increased risk for overall, gastrointestinal, and gynecologic but not lung cancer. VAT but not subcutaneous adipose tissue was associated with risk for overall cancer (HR: 1.22; 95% CI: 1.05-1.43), lung cancer (HR: 1.92; 95% CI: 1.01-3.66), and melanoma (HR: 1.56; 95% CI: 1.02-2.38) independent of BMI. Last, higher CRP levels were associated with higher risk for overall, colorectal, and lung cancer (P < 0.05 for all). Conclusions: Obesity and abdominal adiposity are associated with future risk for specific cancers (eg, gastrointestinal, gynecologic). Although obesity was associated with lower risk for lung cancer, greater VAT and CRP were associated with higher lung cancer risk after adjusting for BMI.

CDKN2C expression in adipose tissue is reduced in type II diabetes and central obesity: impact on adipocyte differentiation and lipid storage?

CDKN2C/p18 (Cyclin-Dependent Kinase Inhibitor 2C) is a cell growth regulator that controls cell cycle progression and has previously been associated with increased risk for type II diabetes (T2D) and reduced peripheral adipose tissue (AT) storage capacity. This study explored the role of CDKN2C in AT lipid and glucose metabolism in T2D. Expression of CDKN2C and other genes was analyzed by transcriptomics, or real-time PCR in subcutaneous AT (SAT) samples obtained from T2D and control subjects matched for sex, age and BMI and also in paired SAT and omental AT (OAT) samples. Functional studies included adipocyte glucose uptake and lipolysis rates. CRISPR/Cas9 CDKN2C gene knockdown was performed in human preadipocytes to assess adipogenesis. CDKN2C mRNA expression in SAT and OAT was reduced in T2D and obese subjects compared to controls. CDKN2C expression in SAT was inversely correlated with measures of hyperglycemia, insulin resistance and visceral adiposity and positively correlated with expression of genes in several metabolic pathways, including insulin signaling and fatty acid and carbohydrate metabolism. CDKN2C protein was mainly expressed in adipocytes compared to stromal vascular cells, and its gene and protein expression was up-regulated during adipocyte differentiation. Knockdown of CDKN2C did not affect the percentage of differentiating cells compared to wild type cultures. However, CDKN2C knockdown cultures had significantly lower expression of differentiation markers CEBPA, ADIPOQ and FASN and transiently reduced lipid accumulation per adipocyte during differentiation. Our findings suggest that adipose CDKN2C expression might be reduced as a consequence of insulin resistance and obesity, and this can further contribute to impairment of SAT lipid storage.

A higher-protein nut-based snack product suppresses glycaemia and decreases glycaemic response to co-ingested carbohydrate in an overweight prediabetic Asian Chinese cohort: the Tu Ora postprandial RCT.

Nut-based products may aid low-glycaemic dietary strategies that are important for diabetes prevention in populations at increased risk of dysglycaemia, such as Asian Chinese. This randomised cross-over trial assessed the postprandial glycaemic response (0-120 min) of a higher-protein nut-based (HP-NB) snack formulation, in bar format (1009 kJ, Nutrient Profiling Score, NPS, -2), when compared with an iso-energetic higher-carbohydrate (CHO) cereal-based bar (HC-CB, 985 kJ, NPS +3). It also assessed the ability to suppress glucose response to a typical CHO-rich food (white bread, WB), when co-ingested. Ten overweight prediabetic Chinese adults (mean, sd: age 47⋅9, 15⋅7 years; BMI 25⋅5, 1⋅6 kg/m2), with total body fat plus ectopic pancreas and liver fat quantified using dual-energy X-ray absorptiometry and magnetic resonance imaging and spectroscopy, received the five meal treatments in random order: HP-NB, HC-CB, HP-NB + WB (50 g available CHO), HC-CB + WB and WB only. Compared with HC-CB, HP-NB induced a significantly lower 30-120 min glucose response (P < 0⋅05), with an approximately 10-fold lower incremental area under the glucose curve (iAUC0-120; P < 0⋅001). HP-NB also attenuated glucose response by approximately 25 % when co-ingested with WB (P < 0⋅05). Half of the cohort had elevated pancreas and/or liver fat, with 13-21 % greater suppression of iAUC0-120 glucose in the low v. high organ fat subgroups across all five treatments. A nut-based snack product may be a healthier alternative to an energy equivalent cereal-based product with evidence of both a lower postprandial glycaemic response and modulation of CHO-induced hyperglycaemia even in high-risk, overweight, pre-diabetic adults.

Weight-loss-independent benefits of exercise on liver steatosis and stiffness in Japanese men with NAFLD.

BACKGROUND & AIMS: A weight-loss-independent beneficial effect of exercise on non-alcoholic fatty liver disease (NAFLD) management has been reported, but the underlying mechanism is unknown. To help determine this mechanism, the effects of exercise on individual tissues (liver, adipose tissue, and skeletal muscle) were retrospectively studied. METHODS: Data from Japanese obese men with NAFLD in a 3-month exercise regimen were analysed and compared with those in a 3-month dietary restriction program designed to achieve weight loss. The underlying mechanism was studied in a smaller subcohort. RESULTS: Independent of the effect of weight loss, the exercise regimen reduced liver steatosis by 9.5% and liver stiffness by 6.8% per 1% weight loss, and resulted in a 16.4% reduction in FibroScan-AST score. Improvements in these hepatic parameters were closely associated with anthropometric changes (reduction in adipose tissue and preservation of muscle mass), increases in muscle strength (+11.6%), reductions in inflammation and oxidative stress (ferritin: -22.3% and thiobarbituric acid: -12.3%), and changes in organokine concentrations (selenoprotein-P: -11.2%, follistatin: +17.1%, adiponectin: +8.9%, and myostatin: -21.6%) during the exercise regimen. Moreover, the expression of target genes of the transcription factor Nrf2, an oxidative stress sensor, was higher in monocytes, suggesting that Nrf2 is activated. Large amounts of high-intensity exercise were effective at further reducing liver steatosis and potentiating improvements in pathophysiological parameters (liver enzyme activities and organokine profiles). CONCLUSIONS: The weight-loss-independent benefits of exercise include anti-steatotic and anti-stiffness effects in the livers of patients with NAFLD. These benefits seem to be acquired through the modification of inter-organ crosstalk, which is characterised by improvements in organokine imbalance and reductions in inflammation and oxidative stress. LAY SUMMARY: We investigated the effects of exercise on non-alcoholic fatty liver disease (NAFLD) that were not related to weight loss. We found that exercise had considerable weight-loss-independent benefits for the liver through a number of mechanisms. This suggests that exercise is important for NAFLD patients, regardless of whether they lose weight.

Impact of maternal central adiposity on infant anthropometry and perinatal morbidity: A systematic review.

Overweight and obesity during pregnancy are risk factors for a large number of perinatal complications, both for the mother and the infant. Risk stratification and early interventions are therefore highly clinically important to minimize future complications. Currently, body mass index (BMI) in early pregnancy is used for risk stratification of pregnant women, but a disadvantage of BMI is that it does not distinguish muscle from fat tissue and central from peripheral adiposity. Maternal fat distribution is suggested to be a better predictor than BMI of obesity-related adverse pregnancy outcomes, with central adiposity posing a greater risk than peripheral subcutaneous fat. With this study, we aimed to systematically review the evidence of what impact maternal central adiposity in early to mid-pregnancy or at most 365 days prior to conception has on infant anthropometry and perinatal morbidity. The databases PubMed/MEDLINE, Web of Science Core Collection, CINAHL, SCOPUS, Clinical Trials, and Open Grey were searched from inception until November 2019. Eligible studies assessed the association between maternal central adiposity, in early to mid-pregnancy or at most 365 days prior to conception, and any of the following infant outcomes: preterm delivery (< 37 weeks of gestation), birthweight, macrosomia, large for gestational age, congenital malformations, hypoglycemia, hyperbilirubinemia, care at neonatal intensive care unit, and death. Two authors independently screened titles and abstracts, read the included full-text studies, and extracted data. The Newcastle-Ottawa Quality Assessment Scale for cohort studies was used to evaluate the quality of and risk of bias in the studies. A total of 720 records were identified, 20 full-text studies assessed for eligibility, and 10 cohort studies included in the review. The results suggest that central adiposity in early to mid-pregnancy or at most 365 days prior to conception may contribute to increased birthweight and increased likelihood of delivery by cesarean section. There is also some evidence of associations between central adiposity and preterm delivery (< 37 weeks of gestation), and admission to neonatal intensive care unit. A meta-analysis was not possible to perform due to substantial heterogeneity among the included studies regarding the exposure, outcome, and statistical methods used. Hence, central adiposity in early to mid-pregnancy or at most 365 days prior to conception could be a possible risk marker in addition to BMI for risk stratification of pregnant women. However, since the topic is only scarcely researched, and the results not unanimous, more studies are needed to further clarify the associations between maternal central adiposity and adverse neonatal complications, before any altered recommendations of guidelines could be made. To enable a future meta-analysis, studies using similar methods for central adiposity assessment,and similar outcome measures, are required.

Comparison between body composition parameters and response to neoadjuvant chemotherapy by using pre-treatment PET CT in locally advanced breast cancer.

PURPOSE: To compare the adipose and muscle tissue areas in patients who responded differently to neoadjuvant chemotherapy. METHODS: One hundred and eighty six patients diagnosed with breast cancer who underwent neoadjuvant chemotherapy between January 2015- October 2019 and were operated after the treatment were retrospectively included in the study. Pathological results were divided into five groups using the Miller-Payne grading systems. Grade 1 indicating no significant reduction in malignant cells; Grade 2: a minor loss of malignant cells (≤ 30 %); Grade 3: reduction in malignant cells between 30 % and 90 %; Grade 4: disappearance of malignant cells >90 %; Grade 5: no malignant cells identifiable. Pre-treatment PET CT scans were evaluated, and calculation of body composition parameters were performed on a single axial section passing through the L3 vertebrae. Spearman's correlation test was used to analyze the correlation between SAT, VAT, MT parameters and pathological responses. RESULTS: There was no strong correlation between the 5 groups separated according to neoadjuvant chemotherapy treatment response and tissue distributions. However, that there was a very low correlation found between superficial adipose tissue and pathological response (r=, 156). CONCLUSION: In conclusion, our results have provided a very low correlation between SAT and more than 30 % response. More research is required to evaluate the role of the body fat and muscle parameters in response to neoadjuvant chemotherapy in larger patient populations.

Hepatic miR-192-3p reactivation alleviates steatosis by targeting glucocorticoid receptor.

BACKGROUND & AIMS: The paradox of hepatic insulin resistance describes the inability for liver to respond to bioenergetics hormones in suppressing gluconeogenesis whilst maintaining lipid synthesis. Here, we report the deficiency of miR-192-3p in the livers of mice with diabetes and its role in alleviating hepatic steatosis. METHODS: As conventional pre-microRNA (miRNA) stem-loop overexpression only boosts guiding strand (i.e. miR-192-5p) expression, we adopted an artificial AAV(DJ)-directed, RNA Pol III promoter-driven miRNA hairpin construct for star-strand-specific overexpression in the liver. Liver steatosis and insulin resistance markers were evaluated in primary hepatocytes, mice with diabetes, and mice with excessive carbohydrate consumption. RESULTS: Functional loss of miR-192-3p in liver exacerbated hepatic micro-vesicular steatosis and insulin resistance in either mice with diabetes or wild-type mice with excessive fructose consumption. Liver-specific overexpression of miR-192-3p effectively halted hepatic steatosis and ameliorated insulin resistance in these mice models. Likewise, hepatocytes overexpressing miR-192-3p exhibited improved lipid accumulation, accompanied with decreases in lipogenesis and lipid-accumulation-related transcripts. Mechanistically, glucocorticoid receptor (GCR, also known as nuclear receptor subfamily 3, group C, member 1 [NR3C1]) was demonstrated to be negatively regulated by miR-192-3p. The effect of miR-192-3p on mitigating micro-vesicular steatosis was ablated by the reactivation of NR3C1. CONCLUSIONS: The star strand miR-192-3p was an undermined glycerolipid regulator involved in controlling fat accumulation and insulin sensitivity in liver through blockade of hepatic GCR signalling; this miRNA may serve as a potential therapeutic option for the common co-mobility of diabetic mellitus and fatty liver disease. LAY SUMMARY: The potential regulatory activity of star strand microRNA (miRNA) species has been substantially underestimated. In this study, we investigate the role and mechanism of an overlooked star strand miRNA (miR-192-3p) in regulating hepatic steatosis and insulin signalling in the livers of mice with diabetes and mice under excessive carbohydrate consumption.

Epicardial fat thickness can predict severity and multivessel distribution in Egyptian patients with atherosclerotic coronary artery stenosis.

BACKGROUND: Epicardial fat, in addition to its secretory function, may have an important role in predicting and stratifying cardiovascular risk. There is a paucity of data regarding correlation between epicardial fat thickness and coronary artery disease in Egypt. AIM OF THE STUDY: To study the relationship between epicardial fat thickness (EFT) measured by trans-thoracic echocardiography (TTE) and severity of coronary artery disease (CAD) and its distribution in Egyptian population. METHODS: Our study was a prospective observational case control study that was conducted upon 150 patients with stable CAD presented to the cardiology departments in Ain Shams University hospitals and Al-Zaitoun Specialized hospital from March to October, 2015. EFT was measured by TTE for all patients at the same day of performing invasive coronary angiography (CA). We studied the statistical correlation between EFT and presence of CAD, also we tried to find if EFT is related to severity of CAD (according to Gensini score) or its distribution. RESULTS: The study population was divided according to CA results to 2 groups; patients' group having atherosclerotic CAD consisting of 100 patients and control group consisting of 50 patients with normal coronaries. All the well- known risk factors of CAD (male sex, smoking, hypertension, diabetes, dyslipidemia, increased body mass index) were significantly more prevalent in the patients' group. Patients had significantly lower systolic and diastolic functions. EFT was significantly correlated to presence of CAD (P < 0.001) with a cut-off value of 5.5 mm. EFT was significantly correlated to severity of CAD assessed by Gensini score (P < 0.001). Also we found a significant positive correlation between EFT and number of vessels affected (P <  0.001). CONCLUSION: EFT is a good predictor of CAD severity and multivessel affection in Egyptian patients. It is also a potentially promising predictor for the presence of CAD.

Body mass index is associated with region-dependent metabolic reprogramming of adipose tissue.

Adipose tissue (AT) is involved in dysmetabolism pathogenesis. Regional fat distribution and functioning may contribute to obesity-related metabolic disorders and adverse health outcomes. Specific fat depots are suggested to possess unique biological properties, but specific metabolic profiles of subcutaneous (SAT) and visceral adipose tissue (VAT) remain unknown. We aimed to characterize VAT and SAT glucose metabolism, and their correlation with body mass index (BMI). AT samples from patients (n = 12; F:M, 9:3) with a mean age of 46 years (26-83 years) and an average BMI of 29.6 kg/m2 (18-37 kg/m2) were used. VAT and SAT explants were obtained during elective laparoscopy, either cholecystectomy for uncomplicated cholelithiasis or gastric bypass for severe obesity. Explants were placed in insulin-free cell culture media and their metabolic profile was established by proton nuclear magnetic resonance. AT explants display a glucose and pyruvate consumption and acetate production that is region-dependent according to the patients BMI. In VAT, glucose consumption was positively correlated with BMI, while alanine and lactate production were negatively correlated with BMI, whereas in SAT the patients BMI did not affect AT secretome suggesting that increased BMI promotes a metabolic reprogramming of VAT towards de novo lipogenesis. This region-dependent metabolic reprogramming of AT associated with BMI was autonomous of insulin. This data, although preliminary, suggests that there is a BMI-related remodeling of glucose metabolism in VAT. Targeting this BMI-induced metabolic shift may represent a potential target to counteract unwanted consequences derived from visceral adiposity.

Study protocol for the FITR Heart Study: Feasibility, safety, adherence, and efficacy of high intensity interval training in a hospital-initiated rehabilitation program for coronary heart disease.

BACKGROUND: For decades, moderate intensity continuous training (MICT) has been the cornerstone of exercise prescription for cardiac rehabilitation (CR). High intensity interval training (HIIT) is now recognized in CR exercise guidelines as an appropriate and efficient modality for improving cardiorespiratory fitness, a strong predictor of mortality. However, the clinical application of HIIT in a real world CR setting, in terms of feasibility, safety, and long-term adherence, needs further investigation to address ongoing reservations. Furthermore, studies using objective measures of exercise intensity (such as heart rate; HR) have produced variable outcomes. Therefore we propose investigating the use of subjective measures (such as rating of perceived exertion (RPE)) for prescribing exercise intensity. METHODS: One hundred adults with coronary artery disease (CAD) attending a hospital-initiated CR program will be randomized to 1) HIIT: 4 × 4 min high intensity intervals at 15-18 RPE interspersed with 3-min active recovery periods or 2) MICT: usual care exercise including 40 min continuous exercise at a moderate intensity corresponding to 11-13 RPE. Primary outcome is change in exercise capacity (peak VO2) following 4 weeks of exercise training. Secondary outcome measures are: feasibility, safety, exercise adherence, body composition, vascular function, inflammatory markers, intrahepatic lipid, energy intake, and dietary behavior over 12-months; and visceral adipose tissue (VAT) following 12 weeks of exercise training. CONCLUSIONS: This study aims to address the ongoing concerns regarding the practicality and safety of HIIT in CR programs. We anticipate study findings will lead to the development of a standardized protocol to facilitate CR programs to incorporate HIIT as a standard exercise option for appropriate patients.

Associations between plasma branched-chain amino acids, ß-aminoisobutyric acid and body composition.

Plasma branched-chain amino acids (BCAA) are elevated in obesity and associated with increased cardiometabolic risk. ß-Aminoisobutyric acid (B-AIBA), a recently identified small molecule metabolite, is associated with decreased cardiometabolic risk. Therefore, we investigated the association of BCAA and B-AIBA with each other and with detailed body composition parameters, including abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). A cross-sectional study was carried out with lean (n 15) and obese (n 33) men and women. Detailed metabolic evaluations, including measures of body composition, insulin sensitivity and plasma metabolomics were completed. Plasma BCAA were higher (1·6 (se 0·08) (×10(7)) v. 1·3 (se 0·06) (×10(7)) arbitrary units; P = 0·005) in obese v. lean subjects. BCAA were positively associated with VAT (R 0·49; P = 0·0006) and trended to an association with SAT (R 0·29; P = 0·052). The association between BCAA and VAT, but not SAT, remained significant after controlling for age, sex and race on multivariate modelling (P < 0·05). BCAA were also associated with parameters of insulin sensitivity (Matsuda index: R -0·50, P = 0·0004; glucose AUC: R 0·53, P < 0·001). BCAA were not associated with B-AIBA (R -0·04; P = 0·79). B-AIBA was negatively associated with SAT (R -0·37; P = 0·01) but only trended to an association with VAT (R 0·27; P = 0·07). However, neither relationship remained significant after multivariate modelling (P > 0·05). Plasma B-AIBA was associated with parameters of insulin sensitivity (Matsuda index R 0·36, P = 0·01; glucose AUC: R -0·30, P = 0·04). Plasma BCAA levels were positively correlated with VAT and markers of insulin resistance. The results suggest a possible complex role of adipose tissue in BCAA homeostasis and insulin resistance.

Application of standards and models in body composition analysis.

The aim of this review is to extend present concepts of body composition and to integrate it into physiology. In vivo body composition analysis (BCA) has a sound theoretical and methodological basis. Present methods used for BCA are reliable and valid. Individual data on body components, organs and tissues are included into different models, e.g. a 2-, 3-, 4- or multi-component model. Today the so-called 4-compartment model as well as whole body MRI (or computed tomography) scans are considered as gold standards of BCA. In practice the use of the appropriate method depends on the question of interest and the accuracy needed to address it. Body composition data are descriptive and used for normative analyses (e.g. generating normal values, centiles and cut offs). Advanced models of BCA go beyond description and normative approaches. The concept of functional body composition (FBC) takes into account the relationships between individual body components, organs and tissues and related metabolic and physical functions. FBC can be further extended to the model of healthy body composition (HBC) based on horizontal (i.e. structural) and vertical (e.g. metabolism and its neuroendocrine control) relationships between individual components as well as between component and body functions using mathematical modelling with a hierarchical multi-level multi-scale approach at the software level. HBC integrates into whole body systems of cardiovascular, respiratory, hepatic and renal functions. To conclude BCA is a prerequisite for detailed phenotyping of individuals providing a sound basis for in depth biomedical research and clinical decision making.

Obesity-associated cancer: an immunological perspective.

Epidemiological studies have established an association between obesity, insulin resistance, type 2 diabetes and a number of cancer types. Research has focused predominantly on altered endocrine factors, growth factors and signalling pathways, with little known in man about the immune involvement in the relevant pathophysiological processes. Moreover, in an era of exciting new breakthroughs in cancer immunotherapy, there is also a need to study the safety and efficacy of immunotherapeutics in the complex setting of inflammatory-driven obesity-associated cancer. This review addresses key immune cell subsets underpinning obesity-associated inflammation and describes how such immune compartments might be targeted to prevent and treat obesity-associated cancer. We propose that the modulation, metabolism, migration and abundance of pro- and anti-inflammatory cells and tumour-specific T cells might be therapeutically altered to both restore immune balance, alleviating pathological inflammation, and to improve anti-tumour immune responses in obesity-associated cancer.