Liver fat response to two days fasting and two days isocaloric high-carbohydrate refeeding in lean and obese women.

Background And Aims: Prolonged fasting, which leads to the mobilization of fat from adipose tissue, can result in the development of hepatosteatosis. However, it is not yet known whether the accumulation of fat in the liver after fasting can be affected by concurrent obesity. Therefore, this study aimed to assess how excessive adiposity influences changes in liver fat content induced by fasting and subsequent refeeding.

Obesity alters adipose tissue response to fasting and refeeding in women: A study on lipolytic and endocrine dynamics and acute insulin resistance.

Fasting induces significant shifts in substrate utilization with signs of acute insulin resistance (IR), while obesity is associated with chronic IR. Nonetheless, both states substantially influence adipose tissue (AT) function. Therefore, in this interventional study (NCT04260542), we investigated if excessive adiposity in premenopausal women alters insulin sensitivity and AT metabolic and endocrine activity in response to a 60-h fast and a subsequent 48-h refeeding period.

The role of adipogenic capacity and dysfunctional subcutaneous adipose tissue in the inheritance of type 2 diabetes mellitus: cross-sectional study.

Objective: This study tested the hypothesis that limited subcutaneous adipose tissue (SAT) expansion represents a primary predisposition to the development of type 2 diabetes mellitus (T2DM), independent of obesity, and identified novel markers of SAT dysfunction in the inheritance of T2DM.

Methods: First-degree relatives (FDR) of T2DM patients (n = 19) and control individuals (n = 19) without obesity (fat mass < 25%) were cross-sectionally compared. Body composition (bioimpedance, computed tomography) and insulin sensitivity (IS; oral glucose tolerance test, clamp) were measured.

Sensitive monitoring of 3-hydroxybutyrate as an indicator of human fasting by capillary electrophoresis in a PAMAMPS coated capillary.

Sensitive electrophoretic determination of 3-hydroxybutyrate (3HB) as an indicator of human ketogenesis is performed in fused silica capillary covalently coated by an anionic copolymer of poly(acrylamide-co-sodium-2-acrylamido-2-methylpropanesulphonate) (PAMAMPS). Baseline separation of 3HB from other components of human serum is achieved in a 20 μm capillary with an effective length of 17 cm covered by 4% PAMAMPS, which generates a cathodic EOF with a mobility of 8.30 ± 0.

Exercise Training Combined with Calanus Oil Supplementation Improves the Central Cardiodynamic Function in Older Women.

The aim of this study was to investigate the possible beneficial effects of exercise training (ET) with omega-3/Calanus oil supplementation on cardiorespiratory and adiposity parameters in elderly women. Fifty-five women (BMI: 19-37 kg/m, 62-80 years old) were recruited and randomly assigned to the 4 month intervention with ET and omega-3 supplementation (Calanus oil, ET-Calanus) or ET and the placebo (sunflower oil; ET-Placebo). The body composition was determined by dual-energy X-ray absorptiometry (DXA), and cardiorespiratory parameters were measured using spiroergometry and PhysioFlow hemodynamic testing.

Lymphedema alters lipolytic, lipogenic, immune and angiogenic properties of adipose tissue: a hypothesis-generating study in breast cancer survivors.

Later stages of secondary lymphedema are associated with the massive deposition of adipose tissue (AT). The factors driving lymphedema-associated AT (LAT) expansion in humans remain rather elusive. We hypothesized that LAT expansion could be based on alterations of metabolic, adipogenic, immune and/or angiogenic qualities of AT.

Signs of Deregulated Gene Expression Are Present in Both CD14 and CD14 PBMC From Non-Obese Men With Family History of T2DM.

Aim: Development of type 2 diabetes (T2DM) is associated with disturbances in immune and metabolic status that may be reflected by an altered gene expression profile of peripheral blood mononuclear cells (PBMC). To reveal a potential family predisposition to these alterations, we investigated the regulation of gene expression profiles in circulating CD14 and CD14 PBMC in fasting conditions and in response to oral glucose tolerance test (OGTT) in glucose tolerant first-degree relatives (FDR) of T2DM patients and in control subjects.

Materials And Methods: This work is based on the clinical study LIMEX (NCT03155412).

Intermittent Hypoxia Stimulates Lipolysis, But Inhibits Differentiation and Lipogenesis in 3T3-L1 Cells.

Exposure to intermittent hypoxia (IH) may play a role in the development of metabolic impairments in the context of obstructive sleep apnea syndrome, probably by elevated plasma levels of free fatty acids. Employing gas-permeable cultureware to grow differentiated human and mouse adipocytes , we directly studied the effects of pericellular oxygen fluctuations on key adipocyte metabolic functions-spontaneous lipolytic rates, triglyceride accumulation, lipogenesis, and expression of adipocyte-specific marker genes. 3T3-L1 fibroblasts and human subcutaneous preadipocytes were differentiated under conditions that induced repetitive pericellular-oxygen cycles IH between 1% O (5 min) and 16% O (5 min), continuously for 14 days or under control conditions.

Circulating Monocyte and Lymphocyte Populations in Healthy First-Degree Relatives of Type 2 Diabetic Patients at Fasting and during Short-Term Hyperinsulinemia.

Aim: The development of type 2 diabetes (T2DM) is associated with disturbances of immune status that may be reflected by alterations of the profile of circulating immune cells. In order to study whether there exists genetic predisposition to these alterations, we investigated the relative content of circulating monocyte and lymphocyte subpopulations at fasting condition and upon stimulation by short-term hyperinsulinemia in nondiabetic first-degree relatives (FDR) of T2DM patients and in control subjects.

Materials And Methods: 19 nondiabetic (FDR) and 19 control subjects without a family history of diabetes (all men) matched for age and BMI underwent 2-hour hyperinsulinemic-euglycemic clamp.

Expression of lipogenic markers is decreased in subcutaneous adipose tissue and adipocytes of older women and is negatively linked to GDF15 expression.

In aging, the capacity of subcutaneous adipose tissue (SAT) to store lipids decreases and this results in metabolically unfavorable fat redistribution. Triggers of this age-related SAT dysfunction may include cellular senescence or endoplasmic reticulum (ER) stress. Therefore, we compared lipogenic capacity of SAT between young and older women and investigated its relation to senescence and ER stress markers.

The Effect of Hypoxia and Metformin on Fatty Acid Uptake, Storage, and Oxidation in L6 Differentiated Myotubes.

Metabolic impairments associated with obstructive sleep apnea syndrome (OSA) are linked to tissue hypoxia, however, the explanatory molecular and endocrine mechanisms remain unknown. Using gas-permeable cultureware, we studied the chronic effects of mild and severe hypoxia on free fatty acid (FFA) uptake, storage, and oxidation in L6 myotubes under 20, 4, or 1% O. Additionally, the impact of metformin and the peroxisome proliferator-activated receptor (PPAR) β/δ agonist, called GW501516, were investigated.

Comparison of Early (2 Days) and Later (28 Days) Response of Adipose Tissue to Very Low-Calorie Diet in Obese Women.

Context: Beneficial metabolic effects of calorie restriction found in the early stage of hypocalorie diets may be caused by the modulation of metabolic and endocrine function of adipose tissue.

Objective: The objective of the study was to compare metabolic and inflammation-related characteristics of sc adipose tissue (SAAT) in the early (2 d) and later (28 d) phase of a very low calorie diet (VLCD). Design, Setting, Intervention, and Patients: Seventeen moderately obese premenopausal women followed an 800 kcal/d VLCD for 28 days.

Adipogenesis, lipogenesis and lipolysis is stimulated by mild but not severe hypoxia in 3T3-L1 cells.

In-vitro investigation of the effects of hypoxia is limited by physical laws of gas diffusion and cellular O2 consumption, making prolonged exposures to stable O2 concentrations impossible. Using a gas-permeable cultureware, chronic effects of mild and severe hypoxia on triglyceride accumulation, lipid droplet size distribution, spontaneous lipolysis and gene expression of adipocyte-specific markers were assessed. 3T3-L1 cells were differentiated under 20%, 4% or 1% O2 using a gas-permeable cultureware.

Acute hyperlipidemia initiates proinflammatory and proatherogenic changes in circulation and adipose tissue in obese women.

Background: Obesity represents a high risk factor for the development of atherosclerosis and is associated with a low-grade inflammation and activation of immune cells.

Aims: The aim of our study was to investigate the effect of a short-term lipid infusion on immune cells in blood and subcutaneous abdominal adipose tissue (SAAT) in obese women.

Methods: Seven-hour intravenous lipid/control infusions were performed in two groups of women (n = 15, n = 10, respectively).

Inhibition of Lipolysis Ameliorates Diabetic Phenotype in a Mouse Model of Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is associated with insulin resistance, glucose intolerance, and type 2 diabetes. Causal mechanisms mediating this association are not well defined; however, augmented lipolysis in adipose might be involved. Here, we investigated the effect of acipimox treatment (lipolysis inhibitor) on glucose tolerance and insulin sensitivity in mice exposed to intermittent hypoxia (IH).

Stress of endoplasmic reticulum modulates differentiation and lipogenesis of human adipocytes.

Background: Adipocytes are cells specialized for storage of neutral lipids. This storage capacity is dependent on lipogenesis and is diminished in obesity. The reason for the decline in lipogenic activity of adipocytes in obesity remains unknown.

Postprandial inflammation is not associated with endoplasmic reticulum stress in peripheral blood mononuclear cells from healthy lean men.

The consumption of lipids and simple sugars induces an inflammatory response whose exact molecular trigger remains elusive. The aims of the present study were to investigate (1) whether inflammation induced by a single high-energy, high-fat meal (HFM) is associated with endoplasmic reticulum stress (ERS) in peripheral blood mononuclear cells (PBMC) and (2) whether these inflammatory and ERS responses could be prevented by the chemical chaperone ursodeoxycholic acid (UDCA). A total of ten healthy lean men were recruited to a randomised, blind, cross-over trial.

Ursodeoxycholic acid but not tauroursodeoxycholic acid inhibits proliferation and differentiation of human subcutaneous adipocytes.

Stress of endoplasmic reticulum (ERS) is one of the molecular triggers of adipocyte dysfunction and chronic low inflammation accompanying obesity. ERS can be alleviated by chemical chaperones from the family of bile acids (BAs). Thus, two BAs currently used to treat cholestasis, ursodeoxycholic and tauroursodeoxycholic acid (UDCA and TUDCA), could potentially lessen adverse metabolic effects of obesity.

Inhibition of vacuolar ATPase attenuates the TRAIL-induced activation of caspase-8 and modulates the trafficking of TRAIL receptosomes.

Tumour necrosis factor (TNF) related apoptosis inducing ligand (TRAIL), a membrane-bound ligand from the TNF family, has attracted significant attention due to its rather specific and effective ability to induce apoptotic death in various types of cancer cells via binding to and activating its pro-apoptotic death receptors. However, a significant number of primary cancer cells often develop resistance to TRAIL treatment, and the signalling platform behind this phenomenon is not fully understood. Upon blocking endosomal acidification by the vacuolar ATPase (V-ATPase) inhibitors bafilomycin A1 (BafA1) or concanamycin A, we observed a significantly reduced initial sensitivity of several, mainly colorectal, tumour cell lines to TRAIL-induced apoptosis.

The plant alkaloid and anti-leukemia drug homoharringtonine sensitizes resistant human colorectal carcinoma cells to TRAIL-induced apoptosis via multiple mechanisms.

TNF-related apoptosis-inducing ligand (TRAIL) is a pro-apoptotic ligand from the TNF-alpha family that is under consideration, along with agonistic anti-TRAIL receptor antibodies, as a potential anti-tumor agent. However, most primary human tumors are resistant to monotherapy with TRAIL apoptogens, and thus the potential applicability of TRAIL in anti-tumor therapy ultimately depends on its rational combination with drugs targeting these resistances. In our high-throughput screening for novel agents/drugs that could sensitize TRAIL-resistant colorectal cancer cells to TRAIL-induced apoptosis, we found homoharringtonine (HHT), a cephalotaxus alkaloid and tested anti-leukemia drug, to be a very effective, low nanomolar enhancer of TRAIL-mediated apoptosis/growth suppression of these resistant cells.

Weight loss improves the adipogenic capacity of human preadipocytes and modulates their secretory profile.

Calorie restriction-induced weight loss is accompanied by profound changes in adipose tissue characteristics. To determine the effect of weight loss on differentiation of preadipocytes and secretory capacity of in vitro differentiated adipocytes, we established cultures of these cells from paired subcutaneous adipose tissue biopsies obtained before and at the end of weight-reducing dietary intervention (DI) in 23 obese women. Based on lipid accumulation and the expression of differentiation markers, in vitro adipogenesis increased after weight loss and it was accompanied by enhanced expression of genes involved in de novo lipogenesis.

TRAIL promotes membrane blebbing, detachment and migration of cells displaying a dysfunctional intrinsic pathway of apoptosis.

Recently, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/Apo2L) has been shown to be a potential candidate for cancer therapy. TRAIL induces apoptosis in various cancer cells but not in normal tissues. Here we show that HCT116 and SW480 cells with a deficient mitochondrial apoptotic pathway were resistant to TRAIL-induced apoptosis, whereas HCT116 and SW480 cells with a functional mitochondrial apoptotic pathway underwent apoptosis upon exposure to TRAIL.

Roscovitine sensitizes leukemia and lymphoma cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a death ligand with selective antitumor activity. However, many primary tumors are TRAIL resistant. Previous studies reported that roscovitine, a cyclin-dependent kinase inhibitor, sensitized various solid cancer cells to TRAIL.