Background: The prevalence of childhood obesity has increased in low- and middle-income countries, including Indonesia. It is important to identify risk factors for cardiovascular disease in obese adolescents in this region.Aim: To assess the risk of metabolic syndrome and early vascular markers for atherosclerosis in obese Indonesian adolescentsMethods: A cross-sectional study was undertaken in obese high school students aged 15-<18 years in Yogyakarta, Indonesia. All eligible adolescents were interviewed about their medical history, were physically examined and had a fasting blood sample taken. Arterial stiffness was measured during systole and diastole blood pressure, endothelial dysfunction was estimated using flow-mediated dilation (FMD) and arterial wall thickness using carotid artery intima-media thickness (CIMT).Results: A total of 4268 students were screened, 298 (7%) of whom were classified as obese. Of those, 229 had blood samples taken, 173 had FMD performed and 156 had CIMT examination. Adolescents with a higher body mass index or BMI Z-score (>3.0) had a significantly poorer lipid profile, insulin level and homeostasis model assessment of insulin resistance (HOMA-IR) than those with a lower BMI Z-score. There were no significant differences for early vasculature markers for atherosclerosis between these two groups.Conclusion: The prevalence of risks of cardiovascular disease in obese adolescents was significant. The higher the BMI Z-score, the higher the risks of cardiovascular disease. Interventions to reduce obesity and its cardiovascular disease morbidities are urgently needed in low- and middle-income countries.Abbreviations: BMI; body mass index; CIMT, carotid artery intima-media thickness; CDC, Centers for Disease Control and Prevention; FMD flow-mediated dilation; HDL high-density lipoprotein cholesterol; HbA1c haemoglobin A1c; HOMA-IR, homeostasis model assessment of insulin resistance; IOTF, International Obesity Task Force; LDL, low-density lipoprotein cholesterol; WHO, World Health Organization.

Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality worldwide. There are well-established screening protocols involving fecal testing, radiographic, and endoscopic evaluations that have led to decreased incidence and mortality of CRC in the United States. In addition to screening for CRC, there is interest in preventing colorectal neoplasia by targeting the signaling pathways that have been identified in the pathway of dysplasia progressing to carcinoma. This review will detail the efficacy of multiple potential preventative strategies including lifestyle changes (physical activity, alcohol use, smoking cessation, and obesity); dietary factors (dietary patterns, calcium, vitamin D, fiber, folate, and antioxidants and micronutrients); and chemopreventive agents (nonsteroidal anti-inflammatory drugs, statins, metformin, bisphosphonates, and postmenopausal hormonal therapy).

Diabetes mellitus is reaching epidemic proportions. In 2014, the total prevalence of diabetes was estimated to be 442 million people worldwide. Due to the aging population and continued increase in obesity rates, the prevalence is expected to rise to 592 million by 2035. Diabetes can lead to several complications, including cardiovascular disease, stroke, peripheral arterial disease, nephropathy, neuropathy, retinopathy, lower extremity amputation and musculoskeletal impairments. Up to 80% of patients referred for outpatient physical therapy have diabetes or are at risk for diabetes. Physical therapists are key members of the healthcare team: prescribing physical activity for the treatment of diabetes and other chronic diseases such as cardiovascular disease and osteoarthritis. Physical therapists can screen for risk factors for diabetes and diabetes-related complications that modify traditional musculoskeletal exercise prescription. Physical therapists must advocate for regular physical activity as a key component for the treatment of chronic diseases in all patient interactions. This report 1) describes the diabetes epidemic and the health impact of diabetes and diabetes-related complications, 2) highlights the physical therapist's role as front-line provider, and 3) provides recommendations for physical therapists in screening for diabetes risk factors and diabetes-related complications and considerations for patient management. We focus on type 2 diabetes. J Orthop Sports Phys Ther, Epub 28 Nov 2019. doi:10.2519/jospt.2020.9154.

Fat-mass and obesity-associated protein (Fto) plays important roles in energy metabolism. It also acts as a demethylase and is most abundantly found in the brain. In the present study, we examined the spatial and temporal changes of Fto immunoreactivity after five minutes of transient forebrain ischemia in the hippocampus. In the control group, Fto immunoreactivity was mainly observed in the nucleus of pyramidal cells in the CA1 and CA3 regions as well as the polymorphic layer, granule cell layer, and subgranular zone of the dentate gyrus. Fto immunoreactivity was transiently, but not significantly, increased in the hippocampal CA3 region and the dentate gyrus two days after ischemia compared to mice without ischemia in the sham-operated group. Four days after ischemia, low Fto immunoreactivity was observed in the stratum pyramidale of the CA1 region because of neuronal death, but Fto immunoreactive cells were abundantly detected in the stratum pyramidale of the CA3 region, which is relatively resistant to ischemic damage. Thereafter, Fto immunoreactivity progressively decreased in the hippocampal CA1 and CA3 regions and the dentate gyrus until ten days after ischemia. At this time-point, Fto immunoreactivity was significantly lower in the hippocampal CA1 and CA3 regions and the dentate gyrus compared to that in the sham-operated group. The reduction of Fto immunoreactive structures in the hippocampus may be associated with impairments in Fto-related hippocampal function.

This study examined associations between a maternal "mixed, high sugar" dietary pattern during pregnancy and ultrasound-determined fetal growth in 495 urban African women and explored whether these associations were independent of maternal baseline body mass index (BMI) and gestational weight gain (GWG). Linear mixed effects modelling (LMM) was used to test the associations between maternal mixed, high sugar dietary pattern score, baseline BMI (kg/m² ), and GWG (kg/week) and the following fetal growth outcomes: (a) biparietal diameter (cm), (b) head circumference (cm), (c) abdominal circumference (cm), and (d) femur length (cm). In the pooled LMM, a +1 standard deviation (SD) increase in the mixed, high sugar dietary pattern score was associated with higher biparietal diameter (0.03 cm/+1 SD; p = .007), head circumference (0.07 cm/+1 SD; p = .026), abdominal circumference (0.08 cm/+1 SD; p = .038), and femur length (0.02 cm/+1 SD; p = .015). Although these associations were independent of maternal BMI and GWG, higher baseline BMI was independently and positively associated with abdominal circumference (0.03 cm/+1 kg/m² ; p = .011) and femur length (0.01 cm/+1 kg/m² ; p = .007) and 1 kg/week greater GWG was associated with a 0.82 cm increase in abdominal circumference (p = .007). In urban African settings, where preconception maternal obesity prevalence is high and processed, high sugar diets are common, improving maternal dietary intake and BMI prior to conception should be prioritised for optimising pregnancy and birth outcomes as well as longer-term offspring health. In addition, dietary management strategies during pregnancy may be beneficial in facilitating healthy fetal growth.

Obesity has become a worldwide health crisis and is associated with a plethora of comorbidities. The multi-organ effects of obesity have been linked to ectopic lipid accumulation. Thus, there is an urgent need to tackle the obesity crisis by developing effective lipid-lowering therapies. 2-hydroxypropyl-β-Cyclodextrin (2HP-β-CD) has been previously shown to reduce lysosomal cholesterol accumulation in a murine model of Niemann Pick Type C (NPC) disease. Using a murine model of Western diet-induced obesity (DIO), we report the effects of 2HP-β-CD in counteracting weight gain, expansion of adipose tissue mass and ectopic lipid accumulation. Interestingly, DIO caused intracellular storage of neutral lipids in hepatic tissues and of phospholipids in kidneys, both of which were prevented by 2HP-β-CD. Importantly, this report brings attention to the nephrotoxic effects of 2HP-β-CD: renal tubular damage, inflammation and fibrosis. These effects may be overlooked, as they are best appreciated upon assessment of renal histology.

Podocytes have foot processes that comprise an important cellular layer of the glomerular barrier involved in regulating glomerular permeability. The disturbance of podocyte function plays a central role in the development of proteinuria in diabetic nephropathy. AMP-activated protein kinase (AMPK), a key regulator of glucose and fatty acid metabolism, plays a major role in obesity and type 2 diabetes. Accumulating evidence suggests that TRPC6 channels are crucial mediators of calcium transport in podocytes, and these channels are involved in disturbing the glomerular filtration barrier in diabetes. Metformin is an anti-diabetic drug widely used for treating patients with type 2 diabetes. Recent studies have suggested that the therapeutic effect of metformin might be mediated by AMPK. The precise function of metformin on cellular function and intracellular signaling in podocytes under diabetic conditions is not fully understood. In this study, we demonstrated that metformin normalized TRPC6 expression via AMPKα1 activation in podocytes exposed to high glucose concentrations. A quantitative analysis showed that metformin increased the colocalization of TRPC6 and AMPKα1 subunits from 42% to 61% in standard glucose (SG) medium and from 29% to 52% in high glucose (HG) medium. AMPK activation was also necessary for maintaining appropriate levels of Rho-family small GTPase activity in HG conditions. Moreover, metformin through AMPK activation remodeled cytoskeleton dynamics, and consequently, reduced filtration barrier permeability in diabetic conditions.

<AbstractText>Glucocorticoids (GCs) are highly effective anti-inflammatory and immunosuppressive drugs. However, prolonged GC therapy may cause numerous adverse effects leading to diabetes and obesity, as well as bone disorders such as osteoporosis in adults and growth retardation in children and adolescents. Prevention and care of the GC-induced adverse effects remain challenging. We have previously demonstrated the efficacy of a treatment with a non-peptidic agonist of adiponectin receptors, AdipoRon, to reverse behaviour disorders and fat mass gain induced by long-term GC treatment. In this work, we have established a relevant model of GC-induced growth and metabolic disorders and determined that AdipoRon is a potential therapeutic tool to reverse these metabolic disturbances.</AbstractText><AbstractText>5-week-old mice were treated continuously with or without corticosterone (35 mg/L) in drinking water for seven consecutive weeks. Taking advantage of this mouse model displaying various growth and metabolic disorders, we assayed whether AdipoRon (daily intraperitoneal injection of 1 mg/kg/day for the last 20 days) might prevent the GC-induced adverse effects. The control group was treated with vehicle only. Nutritional behaviors and metabolic parameters were followed-up throughout the treatment. Serum insulin and leptin levels were measured by ELISA. Computed tomography and histological analysis of adipose tissue were assessed at the end of the experimental procedure.</AbstractText><AbstractText>We found that GC treatment in young mice resulted in continuously increased body weight gain associated with a food intake increase. Compared to vehicle-, GC-treated mice displayed early major hyperleptinemia (up to 6-fold more) and hyperinsulinemia (up to 20-fold more) maintained throughout the treatment. At the end of the experimental procedure, GC-treated mice displayed bone growth retardation (e.g. femur length 15.1 versus 14.0mm, P< 0.01), higher abdominal adipose tissue volume (4.1 versus 2.3, P< 0.01) and altered glucose metabolism compared to control mice. Interestingly, AdipoRon prevented GC-induced effects on energy metabolism such as abdominal adiposity, insulinemia and leptinemia. However, AdipoRon failed to counteract bone growth retardation.</AbstractText><AbstractText>We characterized the very early pathological steps induced by long-term GC in young mice in a relevant model, including growth retardation, fat mass gain and glucose homeostasis dysregulation. The adiponectin system stimulation enabled normalization of the adipose tissue and metabolic features of GC-treated mice. Adiponectin receptor agonists such as AdipoRon might constitute a novel way to counteract some GC-induced adverse effects.</AbstractText>

The importance of overall lipid control in cardiovascular prevention is reviewed. Several studies and meta-analyses show that the control of LDL cholesterol (LDL-C) still maintains a high cardiovascular risk, which is related to the presence of triglyceride-rich lipoproteins, and therefore with an increase in plasma triglycerides and the values of apolipoprotein B (apoB) containing these lipoproteins. The importance of this relationship is due to the change in the lipid profile of our population in recent years. This is related to the increase in obesity and insulin resistance, and is called atherogenic dyslipidaemia. Thus, hypertriglyceridaemia should be considered a cardiovascular risk factor, especially when the desirable objectives of LDL-C have been achieved. The indications for treatment with fibrates in primary and secondary prevention, using the medical evidence-based recommendations, are described, along with its importance in the reduction of cardiovascular risk. Finally, the established indications of the combined statin-fibrate treatment are presented, always after changes in lifestyle.

Mitochondrial dysfunction plays a vital role in the progression of left ventricular hypertrophy (LVH). Previous studies have confirmed that the disorder of SIRT1/PGC-1α deacetylation pathway aggravated mitochondrial dysfunction. HuoXue QianYang QuTan Recipe (HQQR) is a commonly used prescription which has shown therapeutic effects on obesity hypertension and its complications. However, the potential mechanisms are still unclear. In this study, obesity hypertension (OBH) was established in rats and we investigated the efficacy and mechanisms of HQQR on LVH. Rats were divided into the five groups: (1) WKY-ND group, (2) SHR-ND group, (3) OBH-HF group, (4) OBH-HF/V group, (5) OBH-HF/H group. We evaluated body weight, Lee index and blood pressure (BP) before and every 2 weeks after treatment. After 10 weeks of treatment, we mainly detected glycolipid metabolic index, the severity of LVH, mitochondrial function along with SIRT1/PGC-1α deacetylation pathway. Our results showed that HQQR significantly lowered body weight, Lee index, BP and improved the disorder of glycolipid metabolism in OBH rats. Importantly, we uncovered HQQR could alleviate mitochondrial dysfunction in OBH rats by regulating SIRT1/PGC-1α deacetylation pathway. These changes could be associated with the inhibition of LVH.