Is the lack of adiponectin associated with increased ER/SR stress and inflammation in the heart?

Objective To study whether there is an association between adiponectin and endoplasmic reticulum/sarcoplasmic reticulum (ERSR) stress. Research design Eleven-month-old male wild-type (WT) and adiponectin knockout (ADKO) mice were placed on chow or high fat diet for 12 weeks. The changes in ER stress and inflammatory genes were determined in the epididymal adipose, as well as heart tissue of adult WT and ADKO mice.

Reduced kidney lipoprotein lipase and renal tubule triglyceride accumulation in cisplatin-mediated acute kidney injury.

Peroxisome proliferator-activated receptor-α (PPARα) activation attenuates cisplatin (CP)-mediated acute kidney injury by increasing fatty acid oxidation, but mechanisms leading to reduced renal triglyceride (TG) accumulation could also contribute. Here, we investigated the effects of PPARα and CP on expression and enzyme activity of kidney lipoprotein lipase (LPL) as well as on expression of angiopoietin protein-like 4 (Angptl4), glycosylphosphatidylinositol-anchored-HDL-binding protein (GPIHBP1), and lipase maturation factor 1 (Lmf1), which are recognized as important proteins that modulate LPL activity. CP caused a 40% reduction in epididymal white adipose tissue (WAT) mass, with a reduction of LPL expression and activity.

Effect of endoplasmic reticulum stress on inflammation and adiponectin regulation in human adipocytes.

The endoplasmic reticulum (ER) of adipocytes plays a major role in the assembly and secretion of adipokines. The levels of serum adiponectin, secreted by adipocytes, are decreased in insulin resistance, diabetes, and obesity. The role of ER stress in downregulating adiponectin levels has been demonstrated in mouse models of obesity.

The lipoprotein lipase (LPL) S447X gain of function variant involves increased mRNA translation.

Objective: A common gain-of-function LPL variant, LPLS447X, has favorable clinical features and involves a C→G base change at nucleotide 1595 of the LPL cDNA, along with a haplotype, which includes other non-coding SNPs. The mechanism for the LPL gain-in-function is not clear. LPL translation is regulated by epinephrine by an RNA-protein complex, consisting of PKA subunits and an A kinase anchoring protein (AKAP), which targets the 3'UTR.

Regulation of Serum Response Factor and Adiponectin by PPARγ Agonist Docosahexaenoic Acid.

Recent studies indicate that significant health benefits involving the regulation of signaling proteins result from the consumption of omega-3 polyunsaturated fatty acids (ω-3 PUFAs). Serum response factor (SRF) is involved in transcriptional regulation of muscle growth and differentiation. SRF levels are increased in the aging heart muscle.

Obesity and hepatosteatosis in mice with enhanced oxidative DNA damage processing in mitochondria.

Mitochondria play critical roles in oxidative phosphorylation and energy metabolism. Increasing evidence supports that mitochondrial DNA (mtDNA) damage and dysfunction play vital roles in the development of many mitochondria-related diseases, such as obesity, diabetes mellitus, infertility, neurodegenerative disorders, and malignant tumors in humans. Human 8-oxoguanine-DNA glycosylase 1 (hOGG1) transgenic (TG) mice were produced by nuclear microinjection.

Adipose triglyceride lipase expression in human adipose tissue and muscle. Role in insulin resistance and response to training and pioglitazone.

Adipose triglyceride lipase (ATGL) catalyzes the first step in adipocyte and muscle triglyceride hydrolysis, and comparative gene identification-58 (CGI-58) is an essential cofactor. We studied the expression of ATGL and CGI-58 in human adipose and muscle and examined correlations with markers of muscle fatty acid oxidation. Nondiabetic volunteers were studied.

Matrix metalloproteinase-9 is increased in obese subjects and decreases in response to pioglitazone.

Context: The study investigated the regulation of matrix metalloproteinases (MMP)-9 in obesity-associated insulin resistance in humans.

Objectives: The objectives of the investigation were to study MMP-9 regulation by insulin resistance and pioglitazone treatment in impaired glucose tolerant subjects using adipose tissue biopsies and study the mechanism of MMP-9 regulation by pioglitazone in adipocyte cultures.

Research Design: 86 nondiabetic, weight-stable subjects between 21 and 66 yr of age were recruited in a university hospital research center setting.

Adiponectin translation is increased by the PPARgamma agonists pioglitazone and omega-3 fatty acids.

Adiponectin, made exclusively by adipocytes, is a 30-kDa secretory protein assembled posttranslationally into low-molecular weight, middle-molecular weight, and high-molecular weight homo-oligomers. PPARgamma ligand thiozolidinediones, which are widely used in the treatment of type II diabetes, increase adiponectin levels. PPARgamma also has several putative ligands that include fatty acid derivatives.

Stearoyl-coenzyme A desaturase 1 gene expression increases after pioglitazone treatment and is associated with peroxisomal proliferator-activated receptor-gamma responsiveness.

Context And Objective: Stearoyl-coenzyme A desaturase (SCD1) is the rate-limiting enzyme that converts palmitoyl- and stearoyl-coenzyme A to palmitoleoyl- and oleoyl-cownzyme A, respectively. SCD-deficient mice are protected from obesity, and the ob/ob mouse has high levels of SCD. This study was designed to better characterize SCD1 gene and protein expression in humans with varying insulin sensitivity.

Calcium is involved in formation of high molecular weight adiponectin.

Background: Adiponectin, an adipocyte-specific secretory protein, is known to circulate as different isoforms in the blood stream.

Methods: Using sucrose gradients and Western blotting on nondenaturing gels, adiponectin isoforms were examined in human serum, plasma, adipose tissue, and cells. The medium from human adipose tissue and human and mouse adipocytes were also examined for changes in isoform formation upon treatment with EGTA.

Translational regulation of lipoprotein lipase in adipocytes: depletion of cellular protein kinase Calpha activates binding of the C subunit of protein kinase A to the 3'-untranslated region of the lipoprotein lipase mRNA.

Adipose LPL (lipoprotein lipase) plays an important role in regulating plasma triacylglycerols and lipid metabolism. We have previously demonstrated that PKCalpha (protein kinase Calpha) depletion inhibits LPL translation in 3T3-F442A adipocytes. Using in vitro translation experiments, the minimum essential region on the 3'UTR (3'-untranslated region) of LPL mRNA required for the inhibition of translation was identified as the proximal 39 nt.

The lipogenic enzymes DGAT1, FAS, and LPL in adipose tissue: effects of obesity, insulin resistance, and TZD treatment.

Acyl-coenzyme A:diacylglycerol transferase (DGAT), fatty acid synthetase (FAS), and LPL are three enzymes important in adipose tissue triglyceride accumulation. To study the relationship of DGAT1, FAS, and LPL with insulin, we examined adipose mRNA expression of these genes in subjects with a wide range of insulin sensitivity (SI). DGAT1 and FAS (but not LPL) expression were strongly correlated with SI.

Expression of CD68 and macrophage chemoattractant protein-1 genes in human adipose and muscle tissues: association with cytokine expression, insulin resistance, and reduction by pioglitazone.

To examine the role of adipose-resident macrophages in insulin resistance, we examined the gene expression of CD68, a macrophage marker, along with macrophage chemoattractant protein-1 (MCP-1) in human subcutaneous adipose tissue using real-time RT-PCR. Both CD68 and MCP-1 mRNAs were expressed in human adipose tissue, primarily in the stromal vascular fraction. When measured in the adipose tissue from subjects with normal glucose tolerance, covering a wide range of BMI (21-51 kg/m2) and insulin sensitivity (S(I)) (0.

Role of A kinase anchor proteins in the tissue-specific regulation of lipoprotein lipase.

Activation of protein kinase A by catecholamines inhibits lipoprotein lipase (LPL) activity through the elaboration of an RNA binding complex, which inhibits LPL translation by binding to the 3'-untranslated region of the LPL mRNA. To better define this process, we reconstituted the inhibitory RNA binding complex in vitro and demonstrated that the K homology (KH) domain of A kinase anchor protein (AKAP) 121/149 plays a vital role in the inhibition of LPL translation. Inhibition of LPL translation occurred in vitro only when the Calpha subunit, R subunit, and AKAP 149 were present.

Divergent effects of peroxisome proliferator-activated receptor gamma agonists and tumor necrosis factor alpha on adipocyte ApoE expression.

ApoE is expressed in multiple mammalian cell types in which it supports cellular differentiated function. In this report we demonstrate that apoE expression in adipocytes is regulated by factors involved in modulating systemic insulin sensitivity. Systemic treatment with pioglitazone increased systemic insulin sensitivity and increased apoE mRNA levels in adipose tissue by 2-3-fold.

Lipid and carbohydrate metabolism in mice with a targeted mutation in the IL-6 gene: absence of development of age-related obesity.

Obesity-related insulin resistance may be caused by adipokines such as IL-6, which is known to be elevated with the insulin resistance syndrome. A previous study reported that IL-6 knockout mice (IL-6(-/-)) developed maturity onset obesity, with disturbed carbohydrate and lipid metabolism, and increased leptin levels. Because IL-6 is associated with insulin resistance, one might have expected IL-6(-/-) mice to be more insulin sensitive.

Perilipin expression in human adipose tissue is elevated with obesity.

The perilipins are highly phosphorylated adipocyte proteins that are localized at the surface of the lipid droplet. With activation by protein kinase A, perilipins translocate away from the lipid droplet and allow hormone-sensitive lipase to hydrolyze the adipocyte triglycerides to release nonesterified fatty acids (NEFA). Because of the potential importance of adipocyte lipolysis to obesity and insulin resistance, we measured perilipin protein and mRNA levels in nondiabetic subjects with varying degrees of insulin resistance.

Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-alpha expression.

Adiponectin is a 29-kDa adipocyte protein that has been linked to the insulin resistance of obesity and lipodystrophy. To better understand the regulation of adiponectin expression, we measured plasma adiponectin and adipose tissue adiponectin mRNA levels in nondiabetic subjects with varying degrees of obesity and insulin resistance. Plasma adiponectin and adiponectin mRNA levels were highly correlated with each other (r = 0.

Transgenic mice expressing lipoprotein lipase in adipose tissue. Absence of the proximal 3'-untranslated region causes translational upregulation.

Lipoprotein lipase (LPL) is a key enzyme in lipoprotein and adipocyte metabolism. Defects in LPL can lead to hypertriglyceridemia and the subsequent development of atherosclerosis. The mechanisms of regulation of this enzyme are complex and may occur at multiple levels of gene expression.

The translational regulation of lipoprotein lipase by epinephrine involves an RNA binding complex including the catalytic subunit of protein kinase A.

The balance of lipid flux in adipocytes is controlled by the opposing actions of lipolysis and lipogenesis, which are controlled primarily by hormone-sensitive lipase and lipoprotein lipase (LPL), respectively. Catecholamines stimulate adipocyte lipolysis through reversible phosphorylation of hormone-sensitive lipase, and simultaneously inhibit LPL activity. However, LPL regulation is complex and previous studies have described translational regulation of LPL in response to catecholamines because of an RNA-binding protein that interacts with the 3'-untranslated region of LPL mRNA.

Regulation of lipoprotein lipase by protein kinase C alpha in 3T3-F442A adipocytes.

Lipoprotein lipase (LPL) is an important enzyme in adipocyte and lipid metabolism with complex cellular regulation. Previous studies demonstrated an inhibition of LPL activity and synthesis following depletion of protein kinase C (PKC) isoforms with long term treatment of 3T3-F442A adipocytes with 12-O-tetradecanoylphorbol-13-acetate. To identify the specific PKC isoforms involved, we treated cells with antisense oligonucleotides that block expression of specific PKC isoforms.