Elevated Carbohydrate Response Element-Binding Protein Beta (ChREBPβ) and Thioredoxin Interacting Protein (TXNIP) Levels in Human Adipocytes Differentiated in High Glucose Concentrations.

Objectives: Obesity and type 2 diabetes often coexist. The effect of hyperglycemia on adipose tissue is, therefore, of interest. Although studies have shown that high glucose (HG) concentrations do not inhibit adipocyte differentiation, the resulting adipocyte phenotype has not been investigated.

Thyroid-Stimulating Hormone-Stimulated Human Adipocytes Express Thymic Stromal Lymphopoietin.

When recombinant human (rh) thyroid-stimulating hormone (TSH) is administered to thyroid cancer survivors, an acute extra-thyroidal effect raises pro-inflammatory cytokines and activates platelets. Thymic stromal lymphopoietin (TSLP) is a cytokine recently implicated in platelet activation. Our aim was to measure platelet microparticle levels after rhTSH stimulation in vivo, and to investigate TSLP expression in TSH-stimulated human adipocytes in culture.

mTORC1 activates SREBP-2 by suppressing cholesterol trafficking to lysosomes in mammalian cells.

mTORC1 is known to activate sterol regulatory element-binding proteins (SREBPs) including SREBP-2, a master regulator of cholesterol synthesis. Through incompletely understood mechanisms, activated mTORC1 triggers translocation of SREBP-2, an endoplasmic reticulum (ER) resident protein, to the Golgi where SREBP-2 is cleaved to translocate to the nucleus and activate gene expression for cholesterol synthesis. Low ER cholesterol is a well-established trigger for SREBP-2 activation.

The anti-adipogenic effect of peripheral blood mononuclear cells is absent with PCSK9 loss-of-function variants.

Objective: To determine the effect of (1) an oral fat load and (2) pro-protein convertase subtilisin/kexin type (PCSK) 9 loss-of-function (LOF) variant status on the ability of peripheral blood mononuclear cells (PBMC) to inhibit human adipogenesis.

Methods: PBMC from subjects with one or more PCSK9 LOF variants versus non-variant controls were compared in the fasting state and after an oral fat load.

Results: Fasting triglyceride (TG) levels were lower in the LOF variant versus non-variant group but rose to the same level after the oral fat load.

Thyroid-stimulating hormone acutely increases monocyte gene expression in vivo.

Objectives: Thyroid-stimulating hormone (TSH) acts in an extra-thyroidal fashion and induces a pro-inflammatory, pro-coagulant state. Blood monocytes can be activated by vascular stress, but it is not known if this occurs upon TSH administration. Our aim was to determine if recombinant human (rh) TSH, administered acutely to patients being screened for thyroid cancer recurrence, alters blood monocyte gene expression.

Effect of High Glucose Concentration on Human Preadipocytes and Their Response to Macrophage-Conditioned Medium.

Objectives: Adipose tissue expands via differentiation of preadipocytes into adipocytes (adipogenesis) and/or hypertrophy of existing adipocytes. A low adipogenic capacity promotes adipocyte hypertrophy, causing inflammatory macrophage accumulation and insulin resistance. Macrophage-conditioned medium (MacCM) inhibits adipogenesis and promotes adipocyte inflammation, but it is unknown whether these effects are altered by high glucose (HG) versus normal glucose (NG) concentrations.

TSH signaling pathways that regulate MCP-1 in human differentiated adipocytes.

Objective: Adipose tissue is an extra-thyroidal thyroid-stimulating hormone (TSH) target. Increases in lipolysis and in expression and release of interleukin-6 (IL-6) occur in TSH-stimulated adipocytes, and levels of circulating free fatty acids and IL-6 rise following TSH administration to patients with previous thyroidectomy and radioablation for thyroid cancer. Our first objective was to compare how TSH stimulates protein kinase A (PKA) and inhibitor of κB (IκB) kinase (IKK)-β.

Macrophage-induced adipose tissue dysfunction and the preadipocyte: should I stay (and differentiate) or should I go?

Adipose tissue can be regarded as a multidepot organ responsible for metabolic homeostasis by managing sophisticated energy transactions as well as by producing bioactive molecules that regulate insulin sensitivity and immune and vascular responses. Chronic nutrient excess expands adipose tissue, and concomitant variations in its cellular and matrix remodeling can affect the extent of the metabolic dysfunction that is associated with obesity. Preadipocytes, also termed adipose progenitor cells, play a pivotal role in determining whether a dysfunctional hypertrophic state arises as opposed to a hyperplastic process in which mature adipocytes remain relatively responsive.

The activation state of macrophages alters their ability to suppress preadipocyte apoptosis.

Adipose tissue contains macrophages whose state of activation is regulated as obesity develops. Macrophage-secreted factors influence critical processes involved in adipose tissue homeostasis, including preadipocyte proliferation and differentiation into adipocytes. Macrophage-conditioned medium (MacCM) from J774A.

Adipocytes produce aldosterone through calcineurin-dependent signaling pathways: implications in diabetes mellitus-associated obesity and vascular dysfunction.

We reported aldosterone as a novel adipocyte-derived factor that regulates vascular function. We aimed to investigate molecular mechanisms, signaling pathways, and functional significance of adipocyte-derived aldosterone and to test whether adipocyte-derived aldosterone is increased in diabetes mellitus-associated obesity, which contributes to vascular dysfunction. Studies were performed in the 3T3-L1 adipocyte cell line and mature adipocytes isolated from human and mouse (C57BL/6J) adipose tissue.

Macrophage-induced preadipocyte survival depends on signaling through Akt, ERK1/2, and reactive oxygen species.

Obesity is associated with adipose tissue remodeling, characterized by macrophage accumulation, adipocyte hypertrophy, and apoptosis. We previously reported that macrophage-conditioned medium (MacCM) protects preadipocytes from apoptosis, due to serum withdrawal, in a platelet-derived growth factor (PDGF)-dependent manner. We have now investigated the role of intracellular signaling pathways, activated in response to MacCM versus PDGF, in promoting preadipocyte survival.

Effect of collagen I and aortic carboxypeptidase-like protein on 3T3-L1 adipocyte differentiation.

Aortic carboxypeptidase-like protein (ACLP) is a secreted protein expressed in preadipocytes and down-regulated during adipogenesis. Results from previous studies on the influence of ACLP overexpression on adipogenesis vary from no effect to complete inhibition. We hypothesized that ACLP may modulate adipogenesis in the presence of collagen I, a protein to which it binds.

Insulin sensitization of human preadipocytes through glucocorticoid hormone induction of forkhead transcription factors.

Glucocorticoids are synthesized locally in adipose tissue and contribute to metabolic disease through the facilitation of adipose tissue expansion. Here we report that exposure of human primary preadipocytes to glucocorticoids increases their sensitivity to insulin and enhances their subsequent response to stimuli that promote differentiation. This effect was observed in primary human preadipocytes but not in immortalized 3T3-L1 murine preadipocytes or in fully differentiated primary human adipocytes.

IKKbeta and the anti-adipogenic effect of platelet-derived growth factor in human abdominal subcutaneous preadipocytes.

To clarify how anti-adipogenic factors act on preadipocytes to inhibit their differentiation, we compared preadipocyte signaling responses generated by platelet-derived growth factor (PDGF; anti-adipogenic) versus insulin (pro-adipogenic). PDGF, but not insulin, stimulated the phosphorylation of inhibitor of kappaB kinase beta (IKKbeta) in a time-dependent manner. This PDGF-dependent phosphorylation event was inhibited by 60% (P<0.

Macrophage-conditioned medium inhibits differentiation-induced Rb phosphorylation in 3T3-L1 preadipocytes.

This study examines the mechanisms underlying the anti-adipogenic effect of macrophage-secreted products. 3T3-L1 preadipocytes were induced to differentiate over 8 days in medium conditioned by murine J774 macrophages (MacCM). The inhibitory effect on lipid accumulation and expression of adipogenic markers was diminished when addition of MacCM was delayed to day 2 of differentiation.

Measurement of phosphoinositide 3-kinase and its products to study adipogenic signal transduction.

Adipogenesis is an important component of adipose tissue development and growth. Alterations in adipogenesis may promote adipose tissue insulin resistance and inflammation. The ability of preadipocytes to differentiate into mature adipocytes depends on the activation of phosphoinositide 3-kinase (PI3K).

Thyroid-stimulating hormone induces interleukin-6 release from human adipocytes through activation of the nuclear factor-kappaB pathway.

Our objective was to identify the signaling pathway activated by TSH that induces IL-6 secretion from human abdominal sc differentiated adipocytes. Human abdominal sc preadipocytes in culture were differentiated into adipocytes. IL-6 release stimulated by TSH was inhibited by 35% (P < 0.

[Surgical resection of a gastrointestinal stromal cell tumor by double enterectomy and partial pancreatectomy on a 13-year-old mixed breed dog].

Surgical resection of a gastrointestinal stromal cell tumor by double enterectomy and partial pancreatectomy on a 13-year-old mixed breed dog. A 13 year-old, male, mixed breed dog, has been presented for an abdominal mass. The exam showed the presence of an ileo-caeco-colic mass adhered to the distal portion of the pancreas and the mid duodenum.

Aortic carboxypeptidase-like protein is regulated by transforming growth factor beta in 3T3-L1 preadipocytes.

Adipogenesis is characterized by early remodeling of the extracellular matrix, allowing preadipocytes to adopt a more spherical shape and optimize lipid accumulation as they mature. Aortic carboxypeptidase-like protein (ACLP), found in collagen-rich tissues including adipose tissue, is expressed in 3T3-L1 and 3T3-F442A preadipocytes, and is downregulated during adipogenesis. We now report that ACLP is found in medium conditioned by 3T3-L1 preadipocytes.

Activation of the mammalian target of rapamycin pathway acutely inhibits insulin signaling to Akt and glucose transport in 3T3-L1 and human adipocytes.

The mammalian target of rapamycin (mTOR) pathway has recently emerged as a chronic modulator of insulin-mediated glucose metabolism. In this study, we evaluated the involvement of this pathway in the acute regulation of insulin action in both 3T3-L1 and human adipocytes. Insulin rapidly (t(1/2) = 5 min) stimulated the mTOR pathway, as reflected by a 10-fold stimulation of 70-kDa ribosomal S6 kinase 1 (S6K1) activity in 3T3-L1 adipocytes.

Adipogenic and antiapoptotic protein levels in human adipose stromal cells after weight loss.

Objective: Obesity is a major risk factor for type 2 diabetes and cardiovascular disease. However, current strategies to achieve sustained weight loss are often unsuccessful. Fat reaccumulation might be favored by enhanced adipose cell differentiation or survival in the postreduced state.

Apoptosis of human abdominal preadipocytes before and after differentiation into adipocytes in culture.

Differentiation of murine 3T3-L1 preadipocytes into adipocytes is associated with the acquisition of apoptotic resistance accompanied by the upregulation of cell survival genes. We have now examined the effect of adipogenesis on apoptotic susceptibility of human abdominal preadipocytes in primary culture. To induce apoptosis, human preadipocytes, or their differentiated counterparts, were serum-deprived for 24 or 48 hours.

Down-regulation of aortic carboxypeptidase-like protein during the early phase of 3T3-L1 adipogenesis.

Aortic carboxypeptidase-like protein (ACLP) is a 175-kDa protein that is expressed in vascular smooth muscle cells and contains a signal peptide sequence, a lysine- and proline-rich repeating motif, a discoidin-like domain with 35% identity to discoidin I, and a carboxypeptidase-like domain that is 39% identical with carboxypeptidase E. It is secreted into the extracellular matrix and may play a role in abdominal wall development and dermal wound healing. ACLP is also expressed in adipose tissue, but at lower levels.