expression is reduced in human subcutaneous adipose tissue in obesity and type 2 diabetes but may not directly impact adipocyte glucose and lipid metabolism.

Cdk5 and Abl enzyme substrate 1 (CABLES1) is a cell cycle regulator that has previously been identified as a candidate gene for obesity-related phenotypes, but little is known about its role in adipose tissue metabolism. In this study, we explore the role of CABLES1 in obesity and type 2 diabetes (T2D) in human subcutaneous adipose tissue (SAT). We performed gene expression analysis of SAT obtained from subjects with and without T2D, and from a second validation cohort consisting of subjects without T2D.

Palmitate impairs circadian transcriptomics in muscle cells through histone modification of enhancers.

Obesity and elevated circulating lipids may impair metabolism by disrupting the molecular circadian clock. We tested the hypothesis that lipid overload may interact with the circadian clock and alter the rhythmicity of gene expression through epigenomic mechanisms in skeletal muscle. Palmitate reprogrammed the circadian transcriptome in myotubes without altering the rhythmic mRNA expression of core clock genes.

Human adipose tissue gene expression of solute carrier family 19 member 3 (); relation to obesity and weight-loss.

Objective: Adipose tissue is a specialized endocrine organ that is involved in modulating whole-body energy homeostasis and expresses a specific subset of genes, which may play a role in adipose tissue metabolism. The aim of this study was to search for novel adipose tissue-specific genes using a tissue panel of RNAseq expression profiles.

Methods: RNAseq expression profiles from 53 human tissues were downloaded from the GTex database.

Role of Estrogen and Its Receptors in Adipose Tissue Glucose Metabolism in Pre- and Postmenopausal Women.

Context: Reduced estrogen levels in postmenopausal women predispose them to metabolic side effects, including insulin resistance and type 2 diabetes; however, the cellular mechanisms are not well understood.

Objective: This work aimed to study the expression of estrogen receptors in adipose tissue from pre- and postmenopausal women and the effects of estradiol (E2) on glucose uptake of adipocytes.

Methods: Subcutaneous (SAT) and visceral adipose tissue (VAT) obtained from pre- and postmenopausal women (19-51 and 46-75 years old, respectively) were used to measure gene expression of ESR1 and ESR2.

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.

Time Course of Metabolic, Neuroendocrine, and Adipose Effects During 2 Years of Follow-up After Gastric Bypass in Patients With Type 2 Diabetes.

Context: Roux-en-Y gastric bypass surgery (RYGB) markedly improves glycemia in patients with type 2 diabetes (T2D), but underlying mechanisms and changes over time are incompletely understood.

Objective: Integrated assessment of neuroendocrine and metabolic changes over time in T2D patients undergoing RYGB.

Design And Setting: Follow-up of single-center randomized study.

Changes in Circulating Cytokines and Adipokines After RYGB in Patients with and without Type 2 Diabetes.

Objective: This study aimed to compare cytokine and adipokine levels in patients with obesity with and without type 2 diabetes (T2D) at baseline and 6 months after Roux-en-Y gastric bypass (RYGB) with healthy controls.

Methods: A total of 34 patients (21 with T2D) with BMI of 30 to 45 kg/m were compared with 25 healthy controls without obesity. Cytokines, adipokines, and peptides of relevance for inflammation and metabolism were analyzed in plasma.

Altered hormonal and autonomic nerve responses to hypo- and hyperglycaemia are found in overweight and insulin-resistant individuals and may contribute to the development of type 2 diabetes.

Aims/hypothesis: Results from animal models and some clinical work suggest a role for the central nervous system (CNS) in glucose regulation and type 2 diabetes pathogenesis by modulation of glucoregulatory hormones and the autonomic nervous system (ANS). The aim of this study was to characterise the neuroendocrine response to various glucose concentrations in overweight and insulin-resistant individuals compared with lean individuals.

Methods: Overweight/obese (HI, n = 15, BMI ≥27.

Sleep apnea in men is associated with altered lipid metabolism, glucose tolerance, insulin sensitivity, and body fat percentage.

Purpose: Obstructive sleep apnea (OSA) is associated with obesity and risk for type 2 diabetes. In this community-based study, we thoroughly investigated fatty acid metabolism, incretin response, glucose tolerance, insulin secretion and insulin sensitivity, and autonomic nerve activity in men with or without OSA.

Methods: Fifteen men without diabetes but with signs of severe OSA, defined as apnea-hypopnea index (AHI) >30, and 15 age- and BMI-matched men without OSA (AHI < 5) were recruited from a community-based cohort.

Rapid changes in neuroendocrine regulation may contribute to reversal of type 2 diabetes after gastric bypass surgery.

Objective: To explore the role of hormones and the autonomic nervous system in the rapid remission of diabetes after Roux-en-Y Gastric Bypass (RYGB).

Research Design And Methods: Nineteen obese patients with type 2 diabetes, 7 M/12 F, were randomized (2:1) to RYGB or standard-of-care medical treatment (control). At baseline and 4 and 24 weeks post surgery, fasting blood sampling, OGTT, intravenous arginine challenge, and heart-rate variability (HRV) assessments were performed.

Direct effects of glucagon on glucose uptake and lipolysis in human adipocytes.

We aim to investigate the expression of the glucagon receptor (GCGR) in human adipose tissue, and the impact of glucagon in glucose uptake and lipolysis in human adipocytes. GCGR gene expression in human subcutaneous and visceral adipose tissue was demonstrated, albeit at low levels and with an inter-individual variation. Furthermore, GCGR expression was not significantly different between subjects with T2D and matched controls, and we found no significant association with BMI.

Estrogen interacts with glucocorticoids in the regulation of lipocalin 2 expression in human adipose tissue. Reciprocal roles of estrogen receptor α and β in insulin resistance?

The adipokine lipocalin 2 (LCN2) is linked to insulin resistance. Its expression in human adipose tissue (AT) can be regulated in a sex-specific manner by a synthetic glucocorticoid, dexamethasone, suggesting an underlying role of sex steroids. We show that 17-β-estradiol (E2) dose-dependently increased LCN2 gene expression in subcutaneous AT from postmenopausal women.

Early Changes in Adipose Tissue Morphology, Gene Expression, and Metabolism After RYGB in Patients With Obesity and T2D.

Context: Roux-en-Y gastric bypass (RYGB) surgery effectively prevents or treats type 2 diabetes (T2D). Adipose tissue (AT) mechanisms may be of importance.

Objective: To assess the relationship between early changes in whole-body and AT metabolism in surgically treated patients with T2D.

Glucagon Levels During Short-Term SGLT2 Inhibition Are Largely Regulated by Glucose Changes in Patients With Type 2 Diabetes.

Context: The mechanism mediating sodium glucose cotransporter-2 (SGLT2) inhibitor-associated increase in glucagon levels is unknown.

Objective: To assess short-term effects on glucagon, other hormones, and energy substrates after SGLT2 inhibition and whether such effects are secondary to glucose lowering. The impact of adding a dipeptidyl peptidase-4 inhibitor was addressed.

Role of peroxisome proliferator-activated receptor gamma Pro12Ala polymorphism in human adipose tissue: assessment of adipogenesis and adipocyte glucose and lipid turnover.

The protective mechanisms of peroxisome proliferator-activated receptor gamma (PPARγ) Pro12Ala polymorphism in type 2 diabetes (T2D) are unclear. We obtained subcutaneous adipose tissue (AT) before and 3 h after oral glucose (OGTT) in carriers and non-carriers of the Ala allele (12 Pro/Pro, 15 Pro/Ala, and 13 Ala/Ala). Adipogenesis, adipocyte glucose uptake and lipolysis as well as PPARγ target gene expression were investigated and compared between the genotype groups.

A Randomized Controlled Trial of Dapagliflozin Plus Once-Weekly Exenatide Versus Placebo in Individuals with Obesity and Without Diabetes: Metabolic Effects and Markers Associated with Bodyweight Loss.

Introduction: The sodium-glucose cotransporter 2 inhibitor dapagliflozin and the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide reduce bodyweight via differing and complementary mechanisms. This post hoc analysis investigated the metabolic effects and baseline associations with bodyweight loss on coadministration of dapagliflozin and exenatide once weekly (QW) among adults with obesity and without diabetes.

Methods: In the primary trial, adults with obesity and without diabetes [n = 50; 18-70 years; body mass index (BMI) 30-45 kg/m] were randomized to double-blind oral dapagliflozin 10 mg (DAPA) once daily plus subcutaneous long-acting exenatide 2 mg QW (ExQW) or placebo over 24 weeks, followed by an open-label extension from 24-52 weeks during which all participants received active treatment.

Genotype-based recall to study metabolic effects of genetic variation: a pilot study of PPARG Pro12Ala carriers.

Aim: To assess practical implications of genotype-based recall (GBR) studies, an increasingly popular approach for in-depth characterization of genotype-phenotype relationships.

Methods: We genotyped 2500 participants from the Swedish EpiHealth cohort and considered loss-of-function and missense variants in genes with relation to cardiometabolic traits as the basis for our GBR study. Therefore, we focused on carriers and non-carriers of the PPARG Pro12Ala (rs1801282) variant, as it is a relatively common variant with a minor allele frequency (MAF) of 0.

Role of cannabinoid receptor 1 in human adipose tissue for lipolysis regulation and insulin resistance.

We recently showed that the peripheral cannabinoid receptor type 1 (CNR1) gene is upregulated by the synthetic glucocorticoid dexamethasone. CNR1 is highly expressed in the central nervous system and has been a drug target for the treatment of obesity. Here we explore the role of peripheral CNR1 in states of insulin resistance in human adipose tissue.

Lipocalin 2 produces insulin resistance and can be upregulated by glucocorticoids in human adipose tissue.

The adipokine lipocalin 2 is linked to obesity and metabolic disorders. However, its role in human adipose tissue glucose and lipid metabolism is not explored. Here we show that the synthetic glucocorticoid dexamethasone dose-dependently increased lipocalin 2 gene expression in subcutaneous and omental adipose tissue from pre-menopausal females, while it had no effect in post-menopausal females or in males.