scholarly journals Adipose depot-specific effects of ileal interposition surgery in UCD-T2D rats: unexpected implications for obesity and diabetes

2018 ◽  
Vol 475 (3) ◽  
pp. 649-662 ◽  
Author(s):  
Connie Hung ◽  
Casey Bronec ◽  
Eleonora Napoli ◽  
James Graham ◽  
Kimber L. Stanhope ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Plasma Free Fatty Acid ◽  
Diabetic Rats ◽  
Peroxisome Proliferator ◽  
Ileal Interposition ◽  
Peroxisome Proliferator Activated Receptor ◽  
Adipose Depot ◽  
Beneficial Effects ◽  
Obesity And Diabetes

Ileal interposition (IT) surgery delays the onset of diabetes in a rat model of type-2 diabetes (UCD-T2DM). Here, to gain a deeper understanding of the molecular events underlying the effects of IT surgery, we examined the changes in the proteome of four white adipose depots (retroperitoneal, mesenteric, inguinal, and epididymal) and plasma-free fatty acid profile in pre-diabetic rats 1.5 months following IT or sham surgery. The IT-mediated changes were exerted mainly in mesenteric fat and spanned from delayed adipocyte maturation to a neuroendocrine remodeling. Conversely, inguinal, retroperitoneal, and epididymal depots showed opposite trends consistent with increased adipocyte maturation and adipogenesis development prior to overt signs of diabetes, probably orchestrated by peroxisome proliferator-activated receptor gamma signaling and higher plasma n-6/n-3 free fatty acid ratios. The resulting scenario suggests a targeted use of surgical strategies that seek to delay or improve diabetes in order to manipulate adipose depot-specific responses to maximize the duration and beneficial effects of the surgery.

scholarly journals Peroxisome Proliferator-Activated Receptor β/δ (PPARβ/δ) but Not PPARα Serves as a Plasma Free Fatty Acid Sensor in Liver

2010 ◽  
Vol 30 (20) ◽  
pp. 4977-4977
Author(s):  
Linda M. Sanderson ◽  
Tatjana Degenhardt ◽  
Arjen Koppen ◽  
Eric Kalkhoven ◽  
Beatrice Desvergne ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Plasma Free Fatty Acid ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

scholarly journals Peroxisome Proliferator-Activated Receptor β/δ (PPARβ/δ) but Not PPARα Serves as a Plasma Free Fatty Acid Sensor in Liver

2009 ◽  
Vol 29 (23) ◽  
pp. 6257-6267 ◽  
Author(s):  
Linda M. Sanderson ◽  
Tatjana Degenhardt ◽  
Arjen Koppen ◽  
Eric Kalkhoven ◽  
Beatrice Desvergne ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Target Genes ◽  
Plasma Free Fatty Acid ◽  
Functional Differentiation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Plasma Ffa ◽  
Plasma Ffas

ABSTRACT Peroxisome proliferator-activated receptor α (PPARα) is an important transcription factor in liver that can be activated physiologically by fasting or pharmacologically by using high-affinity synthetic agonists. Here we initially set out to elucidate the similarities in gene induction between Wy14643 and fasting. Numerous genes were commonly regulated in liver between the two treatments, including many classical PPARα target genes, such as Aldh3a2 and Cpt2. Remarkably, several genes induced by Wy14643 were upregulated by fasting independently of PPARα, including Lpin2 and St3gal5, suggesting involvement of another transcription factor. Using chromatin immunoprecipitation, Lpin2 and St3gal5 were shown to be direct targets of PPARβ/δ during fasting, whereas Aldh3a2 and Cpt2 were exclusive targets of PPARα. Binding of PPARβ/δ to the Lpin2 and St3gal5 genes followed the plasma free fatty acid (FFA) concentration, consistent with activation of PPARβ/δ by plasma FFAs. Subsequent experiments using transgenic and knockout mice for Angptl4, a potent stimulant of adipose tissue lipolysis, confirmed the stimulatory effect of plasma FFAs on Lpin2 and St3gal5 expression levels via PPARβ/δ. In contrast, the data did not support activation of PPARα by plasma FFAs. The results identify Lpin2 and St3gal5 as novel PPARβ/δ target genes and show that upregulation of gene expression by PPARβ/δ is sensitive to plasma FFA levels. In contrast, this is not the case for PPARα, revealing a novel mechanism for functional differentiation between PPARs.

LOX-1 and inflammation: a new mechanism for renal injury in obesity and diabetes

2008 ◽  
Vol 294 (5) ◽  
pp. F1136-F1145 ◽  
Author(s):  
Katherine J. Kelly ◽  
Pengfei Wu ◽  
Carolyn E. Patterson ◽  
Constance Temm ◽  
Jesus H. Dominguez
Keyword(s):  
Oxidized Ldl ◽  
Lipid Peroxides ◽  
Diabetic Rats ◽  
Peroxisome Proliferator ◽  
Tubulointerstitial Injury ◽  
Peroxisome Proliferator Activated Receptor ◽  
Obesity And Diabetes ◽  
Obese Diabetic Rats

The early nephropathy in obese, diabetic, dyslipidemic (ZS) rats is characterized by tubular lipid accumulation and pervasive inflammation, two critically interrelated events. We now tested the hypothesis that proximal tubules from ZS obese diabetic rats in vivo, and proximal tubule cells (NRK52E) exposed to oxidized LDL (oxLDL) in vitro, change their normally quiescent epithelial phenotype into a proinflammatory phenotype. Urine of obese diabetic rats contained more lipid peroxides, and LOX-1, a membrane receptor that internalizes oxidized lipids, was mobilized to luminal sites. Levels of ICAM-1 and focal adhesion kinase, which participate in leukocyte migration and epithelial dedifferentiation, respectively, were also upregulated in tubules. NRK52E cells exposed to oxLDL showed similar modifications, plus suppression of anti-inflammatory transcription factor peroxisome proliferator-activated receptor-δ. In addition, oxLDL impaired epithelial barrier function. These alterations were prevented by an anti-LOX-1 antibody. The data support the concept that tubular LOX-1 activation driven by lipid oxidants in the preurine fluid is critical in the inflammatory changes. We suggest that luminal lipid oxidants and abnormal tubular permeability may be partly responsible for the renal tubulointerstitial injury of obesity, diabetes, and dyslipidemia.

scholarly journals Enhanced Fatty Acid Flux Triggered by Adiponectin Overexpression

Endocrinology ◽  
2012 ◽  
Vol 153 (1) ◽  
pp. 113-122 ◽  
Author(s):  
Shoba Shetty ◽  
Maria A. Ramos-Roman ◽  
You-Ree Cho ◽  
Jonathan Brown ◽  
Jorge Plutzky ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Uncoupling Protein ◽  
Retinol Binding Protein ◽  
Peroxisome Proliferator ◽  
Tissue Mass ◽  
Triglyceride Synthesis ◽  
Peroxisome Proliferator Activated Receptor ◽  
Brown Adipose

Adiponectin overexpression in mice increases insulin sensitivity independent of adiposity. Here, we combined stable isotope infusion and in vivo measurements of lipid flux with transcriptomic analysis to characterize fatty acid metabolism in transgenic mice that overexpress adiponectin via the aP2-promoter (ADNTg). Compared with controls, fasted ADNTg mice demonstrated a 31% reduction in plasma free fatty acid concentrations (P = 0.008), a doubling of ketones (P = 0.028), and a 68% increase in free fatty acid turnover in plasma (15.1 ± 1.5 vs. 25.3 ± 6.8 mg/kg · min, P = 0.011). ADNTg mice had 2-fold more brown adipose tissue mass, and triglyceride synthesis and turnover were 5-fold greater in this organ (P = 0.046). Epididymal white adipose tissue was slightly reduced, possibly due to the approximately 1.5-fold increase in the expression of genes involved in oxidation (peroxisome proliferator-activated receptor α, peroxisome proliferator-activated receptor-γ coactivator 1α, and uncoupling protein 3). In ADNTg liver, lipogenic gene expression was reduced, but there was an unexpected increase in the expression of retinoid pathway genes (hepatic retinol binding protein 1 and retinoic acid receptor beta and adipose Cyp26A1) and liver retinyl ester content (64% higher, P < 0.02). Combined, these data support a physiological link between adiponectin signaling and increased efficiency of triglyceride synthesis and hydrolysis, a process that can be controlled by retinoids. Interactions between adiponectin and retinoids may underlie adiponectin's effects on intermediary metabolism.

Physical training reverses the increased activity of the hepatic ketone body synthesis pathway in chronically diabetic rats

2006 ◽  
Vol 290 (2) ◽  
pp. E207-E212 ◽  
Author(s):  
Adil El Midaoui ◽  
Jean Louis Chiasson ◽  
Gilles Tancrède ◽  
André Nadeau
Keyword(s):  
Diabetes Mellitus ◽  
Fatty Acid ◽  
Plasma Concentration ◽  
Free Fatty Acid ◽  
Physical Training ◽  
Ketone Body ◽  
Plasma Free Fatty Acid ◽  
Diabetic Rats ◽  
Hydroxybutyric Acid ◽  
Increased Activity

This study was designed to examine whether the training-induced improvement in the plasma concentration of ketone bodies in experimental diabetes mellitus could be explained by changes in the activity of the hepatic ketone body synthesis pathway and/or the plasma free fatty acid levels. Diabetes mellitus was induced by an intravenous injection of streptozotocin (50 mg/kg), and training was carried out on a treadmill. The plasma concentration of β-hydroxybutyric acid was increased ( P < 0.001) in sedentary diabetic rats, and this was partly reversed by training ( P < 0.001). The plasma concentration of free fatty acids was increased ( P < 0.001) in sedentary diabetic rats, and this was reversed to normal by training ( P < 0.001). Diabetes was also associated with an increased activity of the hepatic ketone body synthesis pathway. When the data are expressed as per total liver, physical training decreased the activity of the hepatic ketone body synthesis pathway by 18% in nondiabetic rats ( P < 0.05) and by 22% in diabetic rats ( P < 0.01), the activity present in trained diabetic rats being not statistically different from that of sedentary control rats. These data suggest that the beneficial effects of physical training on the plasma β-hydroxybutyric acid levels in the diabetic state are probably explained in part by a decrease in the activity of the hepatic ketone body synthesis pathway and in part by a decrease in plasma free fatty acid levels.

scholarly journals Mangiferin Improved Palmitate-Induced-Insulin Resistance by Promoting Free Fatty Acid Metabolism in HepG2 and C2C12 Cells via PPARα: Mangiferin Improved Insulin Resistance

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Qiao Zhang ◽  
Xiangju Kong ◽  
Hang Yuan ◽  
Hongjun Guan ◽  
Ying Li ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Glucose Transporter ◽  
C2c12 Cells ◽  
Peroxisome Proliferator ◽  
Glucose Content ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose Transporter 2 ◽  
Ffa Metabolism

Elevated free fatty acid (FFA) is a key risk factor for insulin resistance (IR). Our previous studies found that mangiferin could decrease serum FFA levels in obese rats induced by a high-fat diet. Our research was to determine the effects and mechanism of mangiferin on improving IR by regulating FFA metabolism in HepG2 and C2C12 cells. The model was used to quantify PA-induced lipid accumulation in the two cell lines treated with various concentrations of mangiferin simultaneously for 24 h. We found that mangiferin significantly increased insulin-stimulated glucose uptake, via phosphorylation of protein kinase B (P-AKT), glucose transporter 2 (GLUT2), and glucose transporter 4 (GLUT4) protein expressions, and markedly decreased glucose content, respectively, in HepG2 and C2C12 cells induced by PA. Mangiferin significantly increased FFA uptake and decreased intracellular FFA and triglyceride (TG) accumulations. The activity of the peroxisome proliferator-activated receptor α (PPARα) protein and its downstream proteins involved in fatty acid translocase (CD36) and carnitine palmitoyltransferase 1 (CPT1) and the fatty acid β-oxidation rate corresponding to FFA metabolism were also markedly increased by mangiferin in HepG2 and C2C12 cells. Furthermore, the effects were reversed by siRNA-mediated knockdown of PPARα. Mangiferin ameliorated IR by increasing the consumption of glucose and promoting the FFA oxidation via the PPARα pathway in HepG2 and C2C12 cells.

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