The anti-lipolytic effect of insulin in adipocytes associates with the magnitude of dietary induced weight loss: a longitudinal study.

Background: Insulin resistance is prominent in overweight/obesity. We examined if insulin action in fat cells predicts the outcome of therapeutic weight loss METHODS: We investigated 93 adult Swedes with overweight/obesity (body mass index, BMI, 29-50 kg/m2) before and after hypo-energetic high- or low-fat diet for 10 weeks. At baseline overall insulin resistance (homeostasis model assessment, HOMA-IR), and insulin action on lipolysis and lipogenesis in isolated abdominal subcutaneous fat cells were determined.

Adipose cellularity as a measurement of long-term changes in body weight: a Swedish cohort study spanning 1988-2016.

Background: Adipocyte size and number (cellularity) determine the adipose mass and may relate to long-term body weight changes.

Methods: We investigated 1014 healthy participants at Karolinska Institutet in Sweden 1988-2016 for body weight and size/number of subcutaneous adipocytes, and 273 for visceral adipocyte size. We measured body weight on 281 subjects about 16 years later.

adiposetissue.org: A knowledge portal integrating clinical and experimental data from human adipose tissue.

We developed the Adipose Tissue Knowledge Portal by centralizing previously dispersed datasets, integrating clinical and experimental results with transcriptomic and proteomic data from >6,000 women and men. The platform includes multiple adipose depots, resident cell types, and adipocyte perturbation studies. By providing streamlined data access, the portal enables integrative analyses and serves as a powerful tool to interrogate various dimensions of adipose biology down to the single-cell level.

Decreased Adipose Lipid Turnover Associates With Cardiometabolic Risk and the Metabolic Syndrome.

Background: Disturbed white adipose tissue function is important for cardiometabolic risk and metabolic syndrome (MetS). Whether this involves adipose lipid turnover (lipolysis and synthesis of triglycerides) is unknown and was presently investigated in subcutaneous adipose tissue, the body's largest fat depot.

Methods: In cross-sectional studies in 78 subjects, adipose lipid age, representing overall lipid turnover (mobilization and storage), and lipid storage capacity were assessed by the incorporation of atmospheric C into adipose lipids.

P2Y13 receptor deficiency favors adipose tissue lipolysis and worsens insulin resistance and fatty liver disease.

Excessive lipolysis in white adipose tissue (WAT) leads to insulin resistance (IR) and ectopic fat accumulation in insulin-sensitive tissues. However, the impact of Gi-coupled receptors in restraining adipocyte lipolysis through inhibition of cAMP production remained poorly elucidated. Given that the Gi-coupled P2Y13 receptor (P2Y13-R) is a purinergic receptor expressed in WAT, we investigated its role in adipocyte lipolysis and its effect on IR and metabolic dysfunction-associated steatotic liver disease (MASLD).

Insulin resistance in adipocytes: Novel insights into the pathophysiology of metabolic syndrome.

Background: Insulin resistance in all major target tissues is present in metabolic syndrome (MetS). The resistance in adipocytes is not well described and was presently examined.

Methods: In this observational study on isolated abdominal white subcutaneous adipocytes from 419 adults, concentration-response effects of insulin on lipolysis inhibition (glycerol release) and lipogenesis stimulation (glucose conversion to total lipids) were determined.

Transcriptional determinants of lipid mobilization in human adipocytes.

Defects in adipocyte lipolysis drive multiple aspects of cardiometabolic disease, but the transcriptional framework controlling this process has not been established. To address this, we performed a targeted perturbation screen in primary human adipocytes. Our analyses identified 37 transcriptional regulators of lipid mobilization, which we classified as (i) transcription factors, (ii) histone chaperones, and (iii) mRNA processing proteins.

Adipose Insulin Resistance Associates With Dyslipidemia Independent of Liver Resistance and Involves Early Hormone Signaling.

Background: Adipose tissue insulin resistance is linked to altered plasma levels of triglycerides and HDL (high-density lipoprotein)-cholesterol. However, its degree of independence from liver resistance and different metabolic traits (lipolysis, lipogenesis) effected is not clear and was presently investigated.

Methods: In 3290 adult subjects, plasma levels of triglycerides and HDL-cholesterol were cross-sectionally measured and related to interindividual variations in measures of insulin resistance in the liver (homeostasis mode assessment of insulin resistance index) or adipose tissue (Adipo-IR index).

Adipose tissue specific CCL18 associates with cardiometabolic diseases in non-obese individuals implicating CD4 T cells.

Aim: Obesity is linked to cardiometabolic diseases, however non-obese individuals are also at risk for type 2 diabetes (T2D) and cardiovascular disease (CVD). White adipose tissue (WAT) is known to play a role in both T2D and CVD, but the contribution of WAT inflammatory status especially in non-obese patients with cardiometabolic diseases is less understood. Therefore, we aimed to find associations between WAT inflammatory status and cardiometabolic diseases in non-obese individuals.

A DNA methylation atlas of normal human cell types.

DNA methylation is a fundamental epigenetic mark that governs gene expression and chromatin organization, thus providing a window into cellular identity and developmental processes. Current datasets typically include only a fraction of methylation sites and are often based either on cell lines that underwent massive changes in culture or on tissues containing unspecified mixtures of cells. Here we describe a human methylome atlas, based on deep whole-genome bisulfite sequencing, allowing fragment-level analysis across thousands of unique markers for 39 cell types sorted from 205 healthy tissue samples.

Relationship Between a Sedentary Lifestyle and Adipose Insulin Resistance.

Sedentary people have insulin resistance in their skeletal muscle, but whether this also occurs in fat cells was unknown. Insulin inhibition of hydrolysis of triglycerides (antilipolysis) and stimulation of triglyceride formation (lipogenesis) were investigated in subcutaneous fat cells from 204 sedentary and 336 physically active subjects. Insulin responsiveness (maximum hormone effect) and sensitivity (half-maximal effective concentration) were determined.

Sex-specific regulation of IL-10 production in human adipose tissue in obesity.

Background: Obesity-associated metabolic complications display sexual dimorphism and can be impacted by cytokines. We previously showed that interleukin-10 (IL-10) was upregulated in white adipose tissue (WAT) of obese women with type 2 diabetes (T2D). Whether this pertains to men is unknown.

Lipolysis defect in people with obesity who undergo metabolic surgery.

Objective: Cross-sectional studies demonstrate that catecholamine stimulation of fat cell lipolysis is blunted in obesity. We investigated whether this defect persists after substantial weight loss has been induced by metabolic surgery, and whether it is related to the outcome.

Design/methods: Patients with obesity not able to successfully reduce body weight by conventional means (n = 126) were investigated before and 5 years after Roux-en-Y gastric bypass surgery (RYGB).

The long noncoding RNA ADIPINT regulates human adipocyte metabolism via pyruvate carboxylase.

The pleiotropic function of long noncoding RNAs is well recognized, but their direct role in governing metabolic homeostasis is less understood. Here, we describe a human adipocyte-specific lncRNA, ADIPINT, that regulates pyruvate carboxylase, a pivotal enzyme in energy metabolism. We developed an approach, Targeted RNA-protein identification using Orthogonal Organic Phase Separation, which identifies that ADIPINT binds to pyruvate carboxylase and validated the interaction with electron microscopy.

Long-term improvement of adipocyte insulin action during body weight relapse after bariatric surgery: a longitudinal cohort study.

Background: There are few long-term mechanistic studies in adipose tissue that investigate the metabolic effects of bariatric surgery. Changes in lipogenesis may be involved in long-term weight development.

Objectives: To investigate the long-term effect of bariatric surgery on lipogenesis in abdominal fat cells and whether surgical treatment could induce an epigenetic memory that would maintain improved lipogenesis in spite of body weight relapse.

Shared genetic loci for body fat storage and adipocyte lipolysis in humans.

Total body fat and central fat distribution are heritable traits and well-established predictors of adverse metabolic outcomes. Lipolysis is the process responsible for the hydrolysis of triacylglycerols stored in adipocytes. To increase our understanding of the genetic regulation of body fat distribution and total body fat, we set out to determine if genetic variants associated with body mass index (BMI) or waist-hip-ratio adjusted for BMI (WHRadjBMI) in genome-wide association studies (GWAS) mediate their effect by influencing adipocyte lipolysis.

Subcutaneous adipose tissue expansion mechanisms are similar in early and late onset overweight/obesity.

Background/objective: The development of overweight/obesity associates with alterations in white adipose tissue (WAT) cellularity (fat cell size/number) and lipid metabolism, in particular lipolysis. If these changes differ between early/juvenile (EOO < 18 years of age) or late onset overweight/obesity (LOO) is unknown and was presently examined.

Subjects/methods: We included 439 subjects with validated information on body mass index (BMI) at 18 years of age.

Human white adipose tissue: A highly dynamic metabolic organ.

Recent technological developments have allowed determination of the age of fat cells and their lipids in adult humans. In contrast to prior views, this has demonstrated a high turnover rate of the fat cells (10%/year) and their unilocular lipid droplets (six times/10 years). Fat cell turnover is increased in obesity and when adipose tissue is composed of many but small adipocytes (hyperplasia, a benign adipose phenotype).

Interaction of Diet/Lifestyle Intervention and TCF7L2 Genotype on Glycemic Control and Adiposity among Overweight or Obese Adults: Big Data from Seven Randomized Controlled Trials Worldwide.

. The strongest locus which associated with type 2 diabetes (T2D) by the common variant rs7903146 is the transcription factor 7-like 2 gene (). We aimed to quantify the interaction of diet/lifestyle interventions and the genetic effect of rs7903146 on glycemic traits, body weight, or waist circumference in overweight or obese adults in several randomized controlled trials (RCTs).

A longitudinal study of the antilipolytic effect of insulin in women following bariatric surgery.

Insulin resistance of glucose utilization is fully restored following BMI normalization after bariatric surgery. We investigated if this also pertains to insulin-induced effects on fatty acid handling. Forty-three women with obesity (OB) were investigated before and 2 years after Roux-en-Y gastric by-pass when BMI was <30 kg/m (PO) and compared with 26 never obese women (NO).

An RNAi Screening of Clinically Relevant Transcription Factors Regulating Human Adipogenesis and Adipocyte Metabolism.

Context: Healthy hyperplasic (many but smaller fat cells) white adipose tissue (WAT) expansion is mediated by recruitment, proliferation and/or differentiation of new fat cells. This process (adipogenesis) is controlled by transcriptional programs that have been mostly identified in rodents.

Objective: A systemic investigation of adipogenic human transcription factors (TFs) that are relevant for metabolic conditions has not been revealed previously.