The impact of insulin resistance, gender, genes, glucocorticoids and ethnicity on body fat distribution

The metabolic consequences of obesity are highly dependent on body fat distribution and total body fat mass. Visceral adipose tissue in particular has been found to play an important aetiological role in obesity-related disorders. The contrasting fat distribution between genders, with gynoid and android obesity being characterised by increased subcutaneous and visceral fat deposition respectively, may be directly responsible for differences in obesity-related co-morbidities between the sexes. These differences in adiposity are likely to be directly due to the influence of the sex steroids. Glucocorticoids may further modify body fat distribution, as observed in Cushing’s syndrome in which hypercortisolaemia leads to increased visceral fat mass. Hereditary factors have also been found to be important, with studies demonstrating that up to 55% of the variance in visceral fat mass is genetically determined. Recently, it has been proposed that insulin sensitivity is a major factor that plays a role in determining fat distribution. Although it is accepted that excess adiposity results in insulin resistance, it has been suggested that insulin sensitivity at the level of the adipocyte may modulate the size of the subcutaneous and visceral fat depots. This occurs because insulin resistance retards triglyceride deposition in adipocytes and is therefore associated with reduced adipose tissue growth. It is thought that the subcutaneous depot is the prime site for triglyceride accumulation and, once this depot is lipid replete, triglycerides are diverted to the visceral tissue. The principal determinant of subcutaneous lipid storage capacity is the prevailing level of insulin resistance. This review will discuss all the factors that are thought to influence body fat distribution and will describe the possible role of insulin resistance in this process.Keywords: visceral fat; subcutaneous fat; cortisol; oestrogen; testosteron

Factors predisposing to obesity: a review of the literature

The rising prevalence of obesity is a worldwide problem affecting not only the developed world but also developing nations such as South Africa. Excess body fat deposition is caused by an imbalance between energy intake and energy expenditure and there are many genetic and environmental factors that can influence this balance. The present article will describe these factors and discuss the complex interaction between the environment and the human genome that may underlie the current obesity epidemic.Keywords: obesity, caloric intake, genetic factors, evolutio

Uptake, distribution and elimination of palladium-doped polystyrene nanoplastics in rainbow trout (Oncorhynchus mykiss) following dietary exposure.

The ingestion of nanoplastics (NPs) by fish has led to concerns regarding fish health and food chain transfer, but analytical constraints have hindered quantitative data collection on their uptake and depuration. We used palladium-doped polystyrene nanoplastics (PS-Pd NPs, ~200 nm) to track particle fate in rainbow trout (Oncorhynchus mykiss) during a week-long dietary exposure and subsequent 7-day depuration period on a control diet (no added PS-Pd NPs). At Day 3 and 7 of the exposure, and after depuration, the mid intestine, hind intestine, liver, gallbladder, kidney, gill and carcass were sampled. All organs and the carcass were analysed for total Pd content by inductively couple plasma mass spectrometry. After 3 days of exposure, the mid (32.5 ± 8.3 ng g-1) and hind (42.3 ± 8.2 ng g-1) intestine had significantly higher total Pd concentrations compared to the liver and carcass (1.3 ± 0.4 and 3.4 ± 1.1 ng g-1, respectively). At Day 7, there was no time-related difference in any organ (or the carcass) total Pd concentrations compared to Day 3. When the total Pd content was expressed as a body distribution based on mass of tissue, the carcass contained the highest fraction with 72.5 ± 5.2 % at Day 7, which could raise concerns over transfer to higher trophic levels. The total number of particles that entered the fish over the 7 days was 94.5 ± 13.5 × 106 particles, representing 0.07 ± 0.01 % of the Pd the fish had been fed. Following depuration, there was no detectable Pd in any organ or the carcass, indicating clearance from the fish. These data indicate that these NPs are taken into the internal organs and carcass of fish, yet removal of the exposure results in substantial excretion to below the limit of detection

Lipid accumulation and alkaline phosphatase activity in human preadipocytes isolated from different body fat depots

Background: Alkaline phosphatase (ALP) controls intracellular lipid accumulation in human preadipocytes, but it is not known whether ALP is expressed in all body fat depots, or whether it has a similar role at all sites.Design: Cross-sectional.Setting and subjects: Subjects undergoing breast reduction and abdominal fat biopsies operations at Charlotte Maxeke Johannesburg Academic Hospital.Outcome measures: This study compared intracellular lipid accumulation and ALP activity in the presence and absence of ALP inhibitors in preadipocytes that were obtained from different adipose depots. Abdominal and mammary gland preadipocytes were isolated from women and induced to differentiate in culture. ALP activity and intracellular lipid levels were measured at baseline and after 12 days of differentiation in the presence and absence of the ALP inhibitors, histidine and levamisole.Results: ALP activity was detected in nondifferentiated abdominal (134 ± 7.5 mU/mg protein) and mammary gland (136 ± 9.6 mU/mg protein) preadipocytes. Its activity had increased significantly (p-value < 0.0005 for both) by day 12 of differentiation (388 ± 55 for abdominal and 278 ± 28 mU/mg protein for mammary). Preadipocytes treated with histidine had lower fat accumulation (p-value < 0.0005) and ALP activity (p-value < 0.005) than nontreated cells on day 12, while those treated with levamisole had lower fat accumulation (p-value < 0.005), but elevatedALP activity (p-value < 0.05), compared to nontreated cells. Lipid  accumulation (p-value < 0.005) and ALP activity (p-value < 0.05) were higher in abdominal than mammary gland preadipocytes by day 12.Conclusion: ALP is involved in the control of intracellular lipid accumulation in human preadipocytes that are isolated from both adipose depots. The ability of levamisole to inhibit this process while activating ALP, suggeststhat this molecule acts via an ALP-independent pathway, while histidine attenuates both lipid deposition and ALP activity

Loss of neuronal Miro1 disrupts mitophagy and induces hyperactivation of the integrated stress response

Clearance of mitochondria following damage is critical for neuronal homeostasis. Here, we investigate the role of Miro proteins in mitochondrial turnover by the PINK1/Parkin mitochondrial quality control system in vitro and in vivo. We find that upon mitochondrial damage, Miro is promiscuously ubiquitinated on multiple lysine residues. Genetic deletion of Miro or block of Miro1 ubiquitination and subsequent degradation lead to delayed translocation of the E3 ubiquitin ligase Parkin onto damaged mitochondria and reduced mitochondrial clearance in both fibroblasts and cultured neurons. Disrupted mitophagy in vivo, upon post-natal knockout of Miro1 in hippocampus and cortex, leads to a dramatic increase in mitofusin levels, the appearance of enlarged and hyperfused mitochondria and hyperactivation of the integrated stress response (ISR). Altogether, our results provide new insights into the central role of Miro1 in the regulation of mitochondrial homeostasis and further implicate Miro1 dysfunction in the pathogenesis of human neurodegenerative disease

Limiting weight gain in overweight and obese women during pregnancy to improve health outcomes: the LIMIT randomised controlled trial

Extent: 5p.Background: Obesity is a significant global health problem, with the proportion of women entering pregnancy with a body mass index greater than or equal to 25 kg/m2 approaching 50%. Obesity during pregnancy is associated with a well-recognised increased risk of adverse health outcomes both for the woman and her infant, however there is more limited information available regarding effective interventions to improve health outcomes. The aims of this randomised controlled trial are to assess whether the implementation of a package of dietary and lifestyle advice to overweight and obese women during pregnancy to limit gestational weight gain is effective in improving maternal, fetal and infant health outcomes. Methods/Design: Design: Multicentred randomised, controlled trial. Inclusion Criteria: Women with a singleton, live gestation between 10+0-20+0 weeks who are obese or overweight (defined as body mass index greater than or equal to 25 kg/m2), at the first antenatal visit. Trial Entry & Randomisation: Eligible, consenting women will be randomised between 10+0 and 20+0 weeks gestation using a central telephone randomisation service, and randomisation schedule prepared by non-clinical research staff with balanced variable blocks. Stratification will be according to maternal BMI at trial entry, parity, and centre where planned to give birth. Treatment Schedules: Women randomised to the Dietary and Lifestyle Advice Group will receive a series of inputs from research assistants and research dietician to limit gestational weight gain, and will include a combination of dietary, exercise and behavioural strategies. Women randomised to the Standard Care Group will continue to receive their pregnancy care according to local hospital guidelines, which does not currently include routine provision of dietary, lifestyle and behavioural advice. Outcome assessors will be blinded to the allocated treatment group. Primary Study Outcome: infant large for gestational age (defined as infant birth weight ≥ 90th centile for gestational age). Sample Size: 2,180 women to detect a 30% reduction in large for gestational age infants from 14.40% (p = 0.05, 80% power, two-tailed). Discussion This is a protocol for a randomised trial. The findings will contribute to the development of evidence based clinical practice guidelines.Jodie M Dodd, Deborah A Turnbull, Andrew J McPhee, Gary Wittert, Caroline A Crowther and Jeffrey S Robinso

HIV treatment is associated with a twofold higher probability of raised triglycerides: pooled analyses in 21 023 individuals in sub-Saharan Africa

Background Anti-retroviral therapy (ART) regimes for HIV are associated with raised levels of circulating triglycerides (TGs) in western populations. However, there are limited data on the impact of ART on cardiometabolic risk in sub-Saharan African (SSA) populations. Methods Pooled analyses of 14 studies comprising 21 023 individuals, on whom relevant cardiometabolic risk factors (including TG), HIV and ART status were assessed between 2003 and 2014, in SSA. The association between ART and raised TG (>2.3 mmol/L) was analysed using regression models. Findings Among 10 615 individuals, ART was associated with a two-fold higher probability of raised TG (RR 2.05, 95% CI 1.51–2.77, I2 = 45.2%). The associations between ART and raised blood pressure, glucose, HbA1c, and other lipids were inconsistent across studies. Interpretation Evidence from this study confirms the association of ART with raised TG in SSA populations. Given the possible causal effect of raised TG on cardiovascular disease (CVD), the evidence highlights the need for prospective studies to clarify the impact of long term ART on CVD outcomes in SS

Deriving an optimal threshold of waist circumference for detecting cardiometabolic risk in sub-Saharan Africa.

BACKGROUND: Waist circumference (WC) thresholds derived from western populations continue to be used in sub-Saharan Africa (SSA) despite increasing evidence of ethnic variation in the association between adiposity and cardiometabolic disease and availability of data from African populations. We aimed to derive a SSA-specific optimal WC cut-point for identifying individuals at increased cardiometabolic risk. METHODS: We used individual level cross-sectional data on 24 181 participants aged ⩾15 years from 17 studies conducted between 1990 and 2014 in eight countries in SSA. Receiver operating characteristic curves were used to derive optimal WC cut-points for detecting the presence of at least two components of metabolic syndrome (MS), excluding WC. RESULTS: The optimal WC cut-point was 81.2 cm (95% CI 78.5-83.8 cm) and 81.0 cm (95% CI 79.2-82.8 cm) for men and women, respectively, with comparable accuracy in men and women. Sensitivity was higher in women (64%, 95% CI 63-65) than in men (53%, 95% CI 51-55), and increased with the prevalence of obesity. Having WC above the derived cut-point was associated with a twofold probability of having at least two components of MS (age-adjusted odds ratio 2.6, 95% CI 2.4-2.9, for men and 2.2, 95% CI 2.0-2.3, for women). CONCLUSION: The optimal WC cut-point for identifying men at increased cardiometabolic risk is lower (⩾81.2 cm) than current guidelines (⩾94.0 cm) recommend, and similar to that in women in SSA. Prospective studies are needed to confirm these cut-points based on cardiometabolic outcomes.International Journal of Obesity advance online publication, 31 October 2017; doi:10.1038/ijo.2017.240

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

An Australian Aboriginal birth cohort: a unique resource for a life course study of an Indigenous population. A study protocol

BACKGROUND: The global rise of Type 2 diabetes and its complications has drawn attention to the burden of non-communicable diseases on populations undergoing epidemiological transition. The life course approach of a birth cohort has the potential to increase our understanding of the development of these chronic diseases. In 1987 we sought to establish an Australian Indigenous birth cohort to be used as a resource for descriptive and analytical studies with particular attention on non-communicable diseases. The focus of this report is the methodology of recruiting and following-up an Aboriginal birth cohort of mobile subjects belonging to diverse cultural and language groups living in a large sparsely populated area in the Top End of the Northern Territory of Australia. METHODS: A prospective longitudinal study of Aboriginal singletons born at the Royal Darwin Hospital 1987–1990, with second wave cross-sectional follow-up examination of subjects 1998–2001 in over 70 different locations. A multiphase protocol was used to locate and collect data on 686 subjects with different approaches for urban and rural children. Manual chart audits, faxes to remote communities, death registries and a full time subject locator with past experience of Aboriginal communities were all used. DISCUSSION: The successful recruitment of 686 Indigenous subjects followed up 14 years later with vital status determined for 95% of subjects and examination of 86% shows an Indigenous birth cohort can be established in an environment with geographic, cultural and climatic challenges. The high rates of recruitment and follow up indicate there were effective strategies of follow-up in a supportive population