Asprosin, a novel pleiotropic adipokine implicated in fasting and obesity-related cardio-metabolic disease: Comprehensive review of preclinical and clinical evidence.

White adipose tissue is a dynamic endocrine organ that releases an array of adipokines, which play a key role in regulating metabolic homeostasis and multiple other physiological processes. An altered adipokine secretion profile from adipose tissue depots frequently characterizes obesity and related cardio-metabolic diseases. Asprosin is a recently discovered adipokine that is released in response to fasting. Following secretion, asprosin acts - via an olfactory G-protein coupled receptor and potentially via other unknown receptor(s) - on hepatocytes and agouti-related peptide-expressing neurons in the central nervous system to stimulate glucose secretion and promote appetite, respectively. A growing body of both in vitro and in vivo studies have shown asprosin to exert a number of effects on different metabolic tissues. Indeed, asprosin can attenuate insulin signalling and promote insulin resistance in skeletal muscle by increasing inflammation and endoplasmic reticulum stress. Interestingly, asprosin may also play a protective role in cardiomyocytes that are exposed to hypoxic conditions. Moreover, clinical studies have reported elevated circulating asprosin levels in obesity, type 2 diabetes and other obesity-related cardio-metabolic diseases, with significant associations to clinically relevant parameters. Understanding the spectrum of the effects of this novel adipokine is essential in order to determine its physiologic role and its significance as a potential therapeutic target and/or a biomarker of cardio-metabolic disease. The present review offers a comprehensive overview of the published literature on asprosin, including both clinical and preclinical studies, focusing on its role in metabolism and cardio-metabolic disease.

Exercise, or exercise and diet for the management of polycystic ovary syndrome: a systematic review and meta-analysis.

BACKGROUND: Typically, management of PCOS focuses on lifestyle changes (exercise and diet), aiming to alleviate symptoms, and lower the associated risk of type 2 diabetes and cardiovascular disease. Our objective was to analyse evidence on the effectiveness of exercise in the management of PCOS, when compared to (i) usual care, (ii) diet alone, and (iii) exercise combined with diet, and also exercise combined with diet, compared to (i) control or usual care and (ii) diet alone. METHODS: Relevant databases were searched (June 2017) with no time limit for trial inclusion. Eligible trials employed a randomised or quasi-randomised design to measure the chronic effects of exercise, or exercise and diet in women with PCOS. RESULTS: Searches returned 2390 articles; of those, 27 papers from 18 trials were included. Results are presented as mean difference (MD) and 95% confidence intervals (95% CI). Compared with control, exercise had a statistical effect on change from baseline fasting insulin (MD - 2.44 µIU/mL, 95% CIs - 4.24 to - 0.64; very low-quality evidence), HOMA-IR (- 0.57, - 0.99 to - 0.14; very low-quality evidence), total cholesterol (- 5.88 mg/dL, - 9.92 to - 1.83; low-quality evidence), LDL cholesterol (- 7.39 mg/dL, - 9.83 to - 4.95; low-quality evidence), and triglycerides (- 4.78 mg/dL, - 7.52 to - 2.05; low-quality evidence). Exercise also improved VO2 max (3.84 ml/kg/min, 2.87 to 4.81), waist circumference (- 2.62 cm, - 4.13 to - 1.11), and body fat percentage (- 1.39%, - 2.61 to - 0.18) when compared with usual care. No effect was found for change value systolic/diastolic blood pressure, fasting glucose, HDL cholesterol (all low-quality evidence), or waist-to-hip ratio. Many favourable change score findings were supported by post-intervention value analyses: fasting insulin (- 2.11 µIU/mL, - 3.49 to - 0.73), total cholesterol (- 6.66 mg/dL, - 11.14 to - 2.17), LDL cholesterol (- 6.91 mg/dL, - 12.02 to - 1.80), and VO2 max (5.01 ml/kg/min, 3.48 to 6.54). Statistically lower BMI (- 1.02 kg/m2, - 1.81 to - 0.23) and resting heart rate (- 3.26 beats/min - 4.93 to - 1.59) were also revealed in post-intervention analysis. Subgroup analyses revealed the greatest improvements in overweight/obese participants, and more outcomes improved when interventions were supervised, aerobic in nature, or of a shorter duration. Based on limited data, we found no differences for any outcome between the effects of exercise and diet combined, and diet alone. It was not possible to compare exercise vs diet or exercise and diet combined vs diet. CONCLUSION: Statistically beneficial effects of exercise were found for a range of metabolic, anthropometric, and cardiorespiratory fitness-related outcomes. However, caution should be adopted when interpreting these findings since many outcomes present modest effects and wide CIs, and statistical effects in many analyses are sensitive to the addition/removal of individual trials. Future work should focus on rigorously designed, well-reported trials that make comparisons involving both exercise and diet. SYSTEMATIC REVIEW REGISTRATION: This systematic review was prospectively registered on the Prospero International Prospective Register of Systematic Reviews ( CRD42017062576 ).

Randomised trial of coconut oil, olive oil or butter on blood lipids and other cardiovascular risk factors in healthy men and women.

INTRODUCTION: High dietary saturated fat intake is associated with higher blood concentrations of low-density lipoprotein cholesterol (LDL-C), an established risk factor for coronary heart disease. However, there is increasing interest in whether various dietary oils or fats with different fatty acid profiles such as extra virgin coconut oil may have different metabolic effects but trials have reported inconsistent results. We aimed to compare changes in blood lipid profile, weight, fat distribution and metabolic markers after four weeks consumption of 50 g daily of one of three different dietary fats, extra virgin coconut oil, butter or extra virgin olive oil, in healthy men and women in the general population. DESIGN: Randomised clinical trial conducted over June and July 2017. SETTING: General community in Cambridgeshire, UK. PARTICIPANTS: Volunteer adults were recruited by the British Broadcasting Corporation through their websites. Eligibility criteria were men and women aged 50-75 years, with no known history of cancer, cardiovascular disease or diabetes, not on lipid lowering medication, no contraindications to a high-fat diet and willingness to be randomised to consume one of the three dietary fats for 4 weeks. Of 160 individuals initially expressing an interest and assessed for eligibility, 96 were randomised to one of three interventions; 2 individuals subsequently withdrew and 94 men and women attended a baseline assessment. Their mean age was 60 years, 67% were women and 98% were European Caucasian. Of these, 91 men and women attended a follow-up assessment 4 weeks later. INTERVENTION: Participants were randomised to extra virgin coconut oil, extra virgin olive oil or unsalted butter and asked to consume 50 g daily of one of these fats for 4 weeks, which they could incorporate into their usual diet or consume as a supplement. MAIN OUTCOMES AND MEASURES: The primary outcome was change in serum LDL-C; secondary outcomes were change in total and high-density lipoprotein cholesterol (TC and HDL-C), TC/HDL-C ratio and non-HDL-C; change in weight, body mass index (BMI), waist circumference, per cent body fat, systolic and diastolic blood pressure, fasting plasma glucose and C reactive protein. RESULTS: LDL-C concentrations were significantly increased on butter compared with coconut oil (+0.42, 95% CI 0.19 to 0.65 mmol/L, P<0.0001) and with olive oil (+0.38, 95% CI 0.16 to 0.60 mmol/L, P<0.0001), with no differences in change of LDL-C in coconut oil compared with olive oil (-0.04, 95% CI -0.27 to 0.19 mmol/L, P=0.74). Coconut oil significantly increased HDL-C compared with butter (+0.18, 95% CI 0.06 to 0.30 mmol/L) or olive oil (+0.16, 95% CI 0.03 to 0.28 mmol/L). Butter significantly increased TC/HDL-C ratio and non-HDL-C compared with coconut oil but coconut oil did not significantly differ from olive oil for TC/HDL-C and non-HDL-C. There were no significant differences in changes in weight, BMI, central adiposity, fasting blood glucose, systolic or diastolic blood pressure among any of the three intervention groups. CONCLUSIONS AND RELEVANCE: Two different dietary fats (butter and coconut oil) which are predominantly saturated fats, appear to have different effects on blood lipids compared with olive oil, a predominantly monounsaturated fat with coconut oil more comparable to olive oil with respect to LDL-C. The effects of different dietary fats on lipid profiles, metabolic markers and health outcomes may vary not just according to the general classification of their main component fatty acids as saturated or unsaturated but possibly according to different profiles in individual fatty acids, processing methods as well as the foods in which they are consumed or dietary patterns. These findings do not alter current dietary recommendations to reduce saturated fat intake in general but highlight the need for further elucidation of the more nuanced relationships between different dietary fats and health. TRIAL REGISTRATION NUMBER: NCT03105947; Results.

Plasma irisin is elevated in type 2 diabetes and is associated with increased E-selectin levels.

BACKGROUND: Irisin is a hormone released mainly from skeletal muscle after exercise which increases adipose tissue energy expenditure. Adipocytes can also release irisin after exercise, acting as a local adipokine to induce white adipose tissue to take on a brown adipose tissue-like phenotype, suggesting that irisin and its receptor may represent a novel molecular target for the treatment of obesity and obesity-related diabetes. Previous reports provide conflicting evidence regarding circulating irisin levels in patients with type 2 diabetes (T2DM). METHODS: This study investigated plasma irisin concentrations in 79 T2DM individuals, assessing potential associations with measures of segmental body composition, markers of endothelial dysfunction and peripheral blood mononuclear cell telomere length (TL). RESULTS: Resting, overnight-fasted plasma irisin levels were significantly higher in this group of T2DM patients compared with levels we previously reported in healthy volunteers (p < 0.001). Moreover, plasma irisin displayed a positive correlation with body mass index (p = 0.04), body fat percentage (p = 0.03), HbA1c (p = 0.03) and soluble E-selectin (p < 0.001). A significant negative association was observed between plasma irisin and visceral adiposity (p = 0.006) in T2DM patients. Multiple regression analysis revealed that circulating soluble E-selectin levels could be predicted by plasma irisin (p = 0.004). Additionally, cultured human umbilical vein endothelial cells (HUVEC) exposed to 200 ng/ml irisin for 4 h showed a significant fourfold increase in E-selectin and 2.5-fold increase in ICAM-1 gene expression (p = 0.001 and p = 0.015 respectively), and there was a 1.8-fold increase in soluble E-selectin in conditioned media (p < 0.05). CONCLUSION: These data suggest that elevated plasma irisin in T2DM is associated with indices of adiposity, and that irisin may be involved in pro-atherogenic endothelial disturbances that accompany obesity and T2DM. Accordingly, irisin may constitute a potentially novel therapeutic opportunity in the field of obesity and cardiovascular diabetology.