CDK4-E2F3 signals enhance oxidative skeletal muscle fiber numbers and function to affect myogenesis and metabolism.

Understanding how skeletal muscle fiber proportions are regulated is vital to understanding muscle function. Oxidative and glycolytic skeletal muscle fibers differ in their contractile ability, mitochondrial activity, and metabolic properties. Fiber-type proportions vary in normal physiology and disease states, although the underlying mechanisms are unclear.

Volanesorsen, an antisense oligonucleotide to apolipoprotein C-III, increases lipoprotein lipase activity and lowers triglycerides in partial lipodystrophy.

Background: Partial lipodystrophy (PL) syndromes involve deficiency of adipose tissue, causing severe insulin resistance and hypertriglyceridemia. Apolipoprotein C-III (apoC-III) is elevated in PL and is thought to contribute to hypertriglyceridemia by inhibiting lipoprotein lipase (LPL).

Objective: We hypothesized that volanesorsen, an antisense oligonucleotide to apoC-III, would decrease apoC-III, increase LPL activity, and lower triglycerides in PL.

Insulin sensitivity variations in apparently healthy Arab male subjects: correlation with insulin and C peptide.

Introduction: Decreased insulin sensitivity occurs early in type 2 diabetes (T2D). T2D is highly prevalent in the Middle East and North Africa regions. This study assessed the variations in insulin sensitivity in normal apparently healthy subjects and the levels of adiponectin, adipsin and inflammatory markers.

Core outcomes in gestational diabetes for treatment trials: The Gestational Metabolic Group treatment set.

Aims: With the rising number of outcomes being reported following gestational diabetes (GDM), the outcomes in existing studies vary widely making it challenging to compare and contrast the effectiveness of different interventions for GDM. The purpose of this study was to develop a core outcome and measurement set (COS) for GDM treatment trials.

Materials & Methods: A Delphi study with structured consultation with stakeholders and discussion within a specialist Gestational Metabolic Group (GEM) were combined with a comprehensive systematic search across different databases (PubMed, Cochrane Library, and Embase).

Regulation of circulating CTRP-2/CTRP-9 and GDF-8/GDF-15 by intralipids and insulin in healthy control and polycystic ovary syndrome women following chronic exercise training.

Background: Polycystic ovary syndrome (PCOS) is associated with obesity, diabetes, and insulin resistance. The circulating C1Q/TNF-related proteins (CTRP-2, CTRP-9) and growth differentiation factors (GDF-8, GDF-15) contribute to glucose and lipid homeostasis. The effects of intralipids and insulin infusion on CTRP-2, CTRP-9, GDF-8 and GDF-15 in PCOS and control subjects before and after chronic exercise training were examined.

Prevalence of Hypothyroidism in Patients With Erdheim-Chester Disease.

Importance: Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis affecting multiple organs and commonly caused by somatic pathogenic variants in BRAF V600E and mitogen-activated protein kinase genes. Clinical features of ECD result from histiocytic involvement of various tissues; while endocrine involvement in ECD occurs frequently, the prevalence of central or primary hypothyroidism has not been thoroughly investigated.

Objective: To assess hypothalamus-pituitary-thyroid (HPT) dysfunction in patients with ECD.

Dynamic Changes in Circulating Endocrine FGF19 Subfamily and Fetuin-A in Response to Intralipid and Insulin Infusions in Healthy and PCOS Women.

The fibroblast growth factors (FGF) 19 subfamily, also referred to as endocrine FGFs, includes FGF19, FGF21, and FGF23 are metabolic hormones involved in the regulation of glucose and lipid metabolism. Fetuin-A is a hepatokine involved in the regulation of beta-cell function and insulin resistance. Endocrine FGFs and fetuin-A are dysregulated in metabolic disorders including obesity, type 2 diabetes, non-alcoholic fatty liver disease and polycystic ovary syndrome (PCOS).

Medical and surgical management of obesity and diabetes: what's new?

We conducted a narrative review of the medical and surgical management of people with obesity and diabetes. Results of this review showed that a 5-10% loss in body weight can be achieved with a change in lifestyle, diet and behaviour and with approved pharmacological therapies in people with obesity and diabetes. New targeted therapies are now available for patients with previously untreatable genetic causes of obesity.

Thyroid Hormone Effects on Glucose Disposal in Patients With Insulin Receptor Mutations.

Context: Patients with mutations of the insulin receptor gene (INSR) have extreme insulin resistance and are at risk for early morbidity and mortality from diabetes complications. A case report suggested that thyroid hormone could improve glycemia in INSR mutation in part by increasing brown adipose tissue (BAT) activity and volume.

Objective: To determine if thyroid hormone increases tissue glucose uptake and improves hyperglycemia in INSR mutation.

Adipocyte β-arrestin-2 is essential for maintaining whole body glucose and energy homeostasis.

β-Arrestins are major regulators of G protein-coupled receptor-mediated signaling processes. Their potential roles in regulating adipocyte function in vivo remain unexplored. Here we report the novel finding that mice lacking β-arrestin-2 (barr2) selectively in adipocytes show significantly reduced adiposity and striking metabolic improvements when consuming excess calories.

Lipids and insulin regulate mitochondrial-derived peptide (MOTS-c) in PCOS and healthy subjects.

Objective: Polycystic ovarian syndrome (PCOS) is a heterogeneous endocrine disorder associated with mitochondrial dysfunction and insulin resistance (IR). MOTS-c, a mitochondrial peptide, promotes insulin sensitivity (IS) through activating AKT and AMPK-dependent pathways. The current study was designed to examine the response of MOTS-c to lipids (intralipid) followed by insulin in PCOS and healthy subjects.

Predictive Accuracy of Surrogate Indices for Hepatic and Skeletal Muscle Insulin Sensitivity.

Context: Surrogate indices of muscle and hepatic insulin sensitivity derived from an oral glucose tolerance test (OGTT) are frequently used in clinical studies. However, the predictive accuracy of these indices has not been validated.

Design: In this cross-sectional study, hyperinsulinemic-euglycemic glucose clamp with tritiated glucose infusion and a 75-g OGTT were performed in individuals (n = 659, aged 18 to 49 years, body mass index of 16 to 64 kg/m) with varying degrees of glucose tolerance.

Thyroid Abnormalities in Patients With Extreme Insulin Resistance Syndromes.

Context: Insulin and leptin may increase growth and proliferation of thyroid cells, underlying an association between type 2 diabetes and papillary thyroid cancer (PTC). Patients with extreme insulin resistance due to lipodystrophy or insulin receptor mutations (INSR) are treated with high-dose insulin and recombinant leptin (metreleptin), which may increase the risk of thyroid neoplasia.

Objective: The aim of this study was to analyze thyroid structural abnormalities in patients with lipodystrophy and INSR mutations and to assess whether insulin, IGF-1, and metreleptin therapy contribute to the thyroid growth and neoplasia in this population.

Sweet taste perception is greater in non-Hispanic black than in non-Hispanic white adults.

Objective: Research suggests a difference in sweet taste perception between non-Hispanic black (NHB) and non-Hispanic white (NHW) adults; however, limited research has examined sweet taste perception in relation to the dietary intake of sweet products. The aim of this study was to examine sweet taste perception and the consumption of sweet foods, beverages, and sugar in NHB and NHW adults, and to evaluate whether sweet taste perception is associated with dietary intake.

Methods: This cross-sectional study examined the association between race, sweet taste perception and sweet food, beverages, and sugar consumption in healthy, NHB and NHW adults.

Increased Physical Activity Associated with Less Weight Regain Six Years After "The Biggest Loser" Competition.

Objective: The aim of this study was to explore how physical activity (PA) and energy intake (EI) changes were related to weight loss and regain following "The Biggest Loser" competition.

Methods: At baseline, week 6 and week 30 of the competition, and 6 years after the competition, body composition was measured via dual-energy x-ray absorptiometry, resting energy expenditure was measured by using indirect calorimetry, and EI and PA were measured by using doubly labeled water.

Results: Six years after the competition, median weight loss in 14 of "The Biggest Loser" participants was 13%, with those maintaining a greater weight loss (mean ± SE) of 24.

Results of Screening in Familial Non-Medullary Thyroid Cancer.

Background: Although a family history of thyroid cancer is one of the main risk factors for thyroid cancer, the benefit of screening individuals with a family history of thyroid cancer is not known.

Methods: A prospective cohort study was performed with yearly screening using neck ultrasound and fine-needle aspiration biopsy of thyroid nodule(s) >0.5 cm in at-risk individuals whose relatives were diagnosed with familial non-medullary thyroid cancer (FNMTC).

Metreleptin therapy lowers plasma angiopoietin-like protein 3 in patients with generalized lipodystrophy.

Background: Reduced triglyceride clearance due to impaired lipoprotein lipase-mediated lipolysis contributes to severe hypertriglyceridemia in lipodystrophy. Angiopoietin-like protein 3 (ANGPTL3) and 4 (ANGPTL4) impair clearance of triglycerides by inhibiting lipoprotein lipase. Whether circulating ANGPTL3/4 levels are altered in lipodystrophy and the effects of leptin replacement on these ANGPTLs are unknown.

Plasma serpinB1 is related to insulin sensitivity but not pancreatic -Cell function in non-diabetic adults.

Pancreatic -cell dysfunction because of reduced -cell mass and function is a primary determinant in the progression of diabetes. Increase in -cell mass and compensatory hyperinsulinaemia is frequently associated with insulin-resistant states. Although the humoral factors mediating this compensatory response are unknown, serpinB1, a protease inhibitor, has recently been proposed to be one such factor.

Persistent metabolic adaptation 6 years after "The Biggest Loser" competition.

Objective: To measure long-term changes in resting metabolic rate (RMR) and body composition in participants of "The Biggest Loser" competition.

Methods: Body composition was measured by dual energy X-ray absorptiometry, and RMR was determined by indirect calorimetry at baseline, at the end of the 30-week competition and 6 years later. Metabolic adaptation was defined as the residual RMR after adjusting for changes in body composition and age.

TSH/IGF-1 Receptor Cross Talk in Graves' Ophthalmopathy Pathogenesis.

Context: The TSH receptor (TSHR) is considered the main target of stimulatory autoantibodies in the pathogenesis of Graves' ophthalmopathy (GO); however, it has been suggested that stimulatory IGF-1 receptor (IGF-1R) autoantibodies also play a role.

Objective: We previously demonstrated that a monoclonal stimulatory TSHR antibody, M22, activates TSHR/IGF-1R cross talk in orbital fibroblasts/preadipocytes obtained from patients with GO (GO fibroblasts [GOFs]). We show that cross talk between TSHR and IGF-1R, not direct IGF-1R activation, is involved in the mediation of GO pathogenesis stimulated by Graves' autoantibodies.

Effect of Leptin Administration on Circulating Apolipoprotein CIII levels in Patients With Lipodystrophy.

Context: Apolipoprotein CIII (apoCIII), an inhibitor of lipoprotein lipase, plays an important role in triglyceride metabolism. However, the role of apoCIII in hypertriglyceridemia in lipodystrophy and the effects of leptin replacement on apoCIII levels are unknown.

Objective: The objective of the study was to test the hypotheses that apoCIII is elevated in hypertriglyceridemic patients with lipodystrophy and that leptin replacement in these patients lowers circulating apoCIII.