Diabetes, lipids, and adipocyte secretagogues

2004 ◽  
Vol 82 (1) ◽  
pp. 170-190 ◽  
Author(s):  
May Faraj ◽  
Hui Ling Lu ◽  
Katherine Cianflone
Keyword(s):  
Diabetes Mellitus ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
White Adipose Tissue ◽  
Insulin Response ◽  
Type Ii Diabetes Mellitus ◽  
Insulin Resistant ◽  
Glucose And Lipid Metabolism ◽  
Obesity And Diabetes ◽  
Factor Α

That obesity is associated with insulin resistance and type II diabetes mellitus is well accepted. Overloading of white adipose tissue beyond its storage capacity leads to lipid disorders in non-adipose tissues, namely skeletal and cardiac muscles, pancreas, and liver, effects that are often mediated through increased non-esterified fatty acid fluxes. This in turn leads to a tissue-specific disordered insulin response and increased lipid deposition and lipotoxicity, coupled to abnormal plasma metabolic and (or) lipoprotein profiles. Thus, the importance of functional adipocytes is crucial, as highlighted by the disorders seen in both "too much" (obesity) and "too little" (lipodystrophy) white adipose tissue. However, beyond its capacity for fat storage, white adipose tissue is now well recognised as an endocrine tissue producing multiple hormones whose plasma levels are altered in obese, insulin-resistant, and diabetic subjects. The consequence of these hormonal alterations with respect to both glucose and lipid metabolism in insulin target tissues is just beginning to be understood. The present review will focus on a number of these hormones: acylation-stimulating protein, leptin, adiponectin, tumour necrosis factor α, interleukin-6, and resistin, defining their changes induced in obesity and diabetes mellitus and highlighting their functional properties that may protect or worsen lipid metabolism.Key words: C3adesarg, fatty acid trapping, lipolysis, lipogenesis.

Molecular and metabolic profiles suggest that increased lipid catabolism in adipose tissue contributes to leanness in domestic chickens

2014 ◽  
Vol 46 (9) ◽  
pp. 315-327 ◽  
Author(s):  
Bo Ji ◽  
Jesse L. Middleton ◽  
Ben Ernest ◽  
Arnold M. Saxton ◽  
Susan J. Lamont ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
White Adipose Tissue ◽  
Broiler Chickens ◽  
Acid Oxidation ◽  
Human Obesity ◽  
Insulin Resistant ◽  
Expression Of Genes ◽  
Commercial Broiler

Domestic broiler chickens rapidly accumulate fat and are naturally hyperglycemic and insulin resistant, making them an attractive model for studies of human obesity. We previously demonstrated that short-term (5 h) fasting rapidly upregulates pathways of fatty acid oxidation in broiler chickens and proposed that activation of these pathways may promote leanness. The objective of the current study was to characterize adipose tissue from relatively lean and fatty lines of chickens and determine if heritable leanness in chickens is associated with activation of some of the same pathways induced by fasting. We compared adipose gene expression and metabolite profiles in white adipose tissue of lean Leghorn and Fayoumi breeds to those of fattier commercial broiler chickens. Both lipolysis and expression of genes involved in fatty acid oxidation were upregulated in lean chickens compared with broilers. Although there were strong similarities between the lean lines compared with broilers, distinct expression signatures were also found between Fayoumi and Leghorn, including differences in adipogenic genes. Similarities between genetically lean and fasted chickens suggest that fatty acid oxidation in white adipose tissue is adaptively coupled to lipolysis and plays a role in heritable differences in fatness. Unique signatures of leanness in Fayoumi and Leghorn lines highlight distinct pathways that may provide insight into the basis for leanness in humans. Collectively, our results provide a number of future directions through which to fully exploit chickens as unique models for the study of human obesity and adipose metabolism.

scholarly journals Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Anastasia Georgiadi ◽  
Valeria Lopez-Salazar ◽  
Rabih El- Merahbi ◽  
Rhoda Anane Karikari ◽  
Xiaochuan Ma ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Dependent Manner ◽  
Metabolic Dysfunction ◽  
Functional Interaction ◽  
White Adipocyte ◽  
White Adipocytes ◽  
Obesity And Diabetes ◽  
Adhesion Gpcr ◽  
Circulating Levels

AbstractThe proper functional interaction between different tissues represents a key component in systemic metabolic control. Indeed, disruption of endocrine inter-tissue communication is a hallmark of severe metabolic dysfunction in obesity and diabetes. Here, we show that the FNDC4-GPR116, liver-white adipose tissue endocrine axis controls glucose homeostasis. We found that the liver primarily controlled the circulating levels of soluble FNDC4 (sFNDC4) and lowering of the hepatokine FNDC4 led to prediabetes in mice. Further, we identified the orphan adhesion GPCR GPR116 as a receptor of sFNDC4 in the white adipose tissue. Upon direct and high affinity binding of sFNDC4 to GPR116, sFNDC4 promoted insulin signaling and insulin-mediated glucose uptake in white adipocytes. Indeed, supplementation with FcsFNDC4 in prediabetic mice improved glucose tolerance and inflammatory markers in a white-adipocyte selective and GPR116-dependent manner. Of note, the sFNDC4-GPR116, liver-adipose tissue axis was dampened in (pre) diabetic human patients. Thus our findings will now allow for harnessing this endocrine circuit for alternative therapeutic strategies in obesity-related pre-diabetes.

scholarly journals Exercise training enhances white adipose tissue metabolism in rats selectively bred for low- or high-endurance running capacity

2013 ◽  
Vol 305 (3) ◽  
pp. E429-E438 ◽  
Author(s):  
Erin J. Stephenson ◽  
Sarah J. Lessard ◽  
Donato A. Rivas ◽  
Matthew J. Watt ◽  
Ben B. Yaspelkis ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Exercise Training ◽  
White Adipose Tissue ◽  
Citrate Synthase ◽  
Mitochondrial Protein ◽  
Treadmill Running ◽  
Endurance Running ◽  
Insulin Resistant ◽  
Disease States ◽  
Hcr Model

Impaired visceral white adipose tissue (WAT) metabolism has been implicated in the pathogenesis of several lifestyle-related disease states, with diminished expression of several WAT mitochondrial genes reported in both insulin-resistant humans and rodents. We have used rat models selectively bred for low- (LCR) or high-intrinsic running capacity (HCR) that present simultaneously with divergent metabolic phenotypes to test the hypothesis that oxidative enzyme expression is reduced in epididymal WAT from LCR animals. Based on this assumption, we further hypothesized that short-term exercise training (6 wk of treadmill running) would ameliorate this deficit. Approximately 22-wk-old rats (generation 22) were studied. In untrained rats, the abundance of mitochondrial respiratory complexes I–V, citrate synthase (CS), and PGC-1 was similar for both phenotypes, although CS activity was greater than 50% in HCR ( P = 0.09). Exercise training increased CS activity in both phenotypes but did not alter mitochondrial protein content. Training increased the expression and phosphorylation of proteins with roles in β-adrenergic signaling, including β3-adrenergic receptor (16% increase in LCR; P < 0.05), NOR1 (24% decrease in LCR, 21% decrease in HCR; P < 0.05), phospho-ATGL (25% increase in HCR; P < 0.05), perilipin (25% increase in HCR; P < 0.05), CGI-58 (15% increase in LCR; P < 0.05), and GLUT4 (16% increase in HCR; P < 0.0001). A training effect was also observed for phospho-p38 MAPK (12% decrease in LCR, 20% decrease in HCR; P < 0.05) and phospho-JNK (29% increase in LCR, 20% increase in HCR; P < 0.05). We conclude that in the LCR-HCR model system, mitochondrial protein expression in WAT is not affected by intrinsic running capacity or exercise training. However, training does induce alterations in the activity and expression of several proteins that are essential to the intracellular regulation of WAT metabolism.

scholarly journals Metabolism and secretory function of white adipose tissue: effect of dietary fat

2009 ◽  
Vol 81 (3) ◽  
pp. 453-466 ◽  
Author(s):  
Cláudia M. Oller do Nascimento ◽  
Eliane B. Ribeiro ◽  
Lila M. Oyama
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
White Adipose Tissue ◽  
Dietary Fat ◽  
Dietary Fatty Acids ◽  
Secretory Function ◽  
High Fat ◽  
Adipose Tissue Metabolism ◽  
Tissue Metabolism

Approximately 40% of the total energy consumed by western populations is represented by lipids, most of them being ingested as triacylglycerols and phospholipids. The focus of this review is to analyze the effect of the type of dietary fat on white adipose tissue metabolism and secretory function, particularly on haptoglobin, TNF-α, plasminogen activator inhibitor-1 and adiponectin secretion. Previous studies have demonstrated that the duration of the exposure to the high-fat feeding, amount of fatty acid present in the diet and the type of fatty acid may or may not have a significant effect on adipose tissue metabolism. However, the long-term or short-term high fat diets, especially rich in saturated fatty acids, probably by activation of toll-like receptors, stimulated the expression of proinflammatory adipokines and inhibited adiponectin expression. Further studies are needed to investigate the cellular mechanisms by which dietary fatty acids affect white adipose tissue metabolism and secretory functions.

scholarly journals Role of Arginase 2 in Systemic Metabolic Activity and Adipose Tissue Fatty Acid Metabolism in Diet-Induced Obese Mice

2019 ◽  
Vol 20 (6) ◽  
pp. 1462 ◽  
Author(s):  
Reem Atawia ◽  
Haroldo Toque ◽  
Mohamed Meghil ◽  
Tyler Benson ◽  
Nicole Yiew ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Normal Diet ◽  
Metabolic Dysfunction ◽  
Ppar Γ ◽  
Obesity And Diabetes ◽  
Visceral Adipose ◽  
Upregulated Genes

Visceral adipose tissue (VAT) inflammation and metabolic dysregulation are key components of obesity-induced metabolic disease. Upregulated arginase, a ureahydrolase enzyme with two isoforms (A1-cytosolic and A2-mitochondrial), is implicated in pathologies associated with obesity and diabetes. This study examined A2 involvement in obesity-associated metabolic and vascular disorders. WT and globally deleted A2(−/−) or A1(+/−) mice were fed either a high fat/high sucrose (HFHS) diet or normal diet (ND) for 16 weeks. Increases in body and VAT weight of HFHS-fed WT mice were abrogated in A2−/−, but not A1+/−, mice. Additionally, A2−/− HFHS-fed mice exhibited higher energy expenditure, lower blood glucose, and insulin levels compared to WT HFHS mice. VAT and adipocytes from WT HFHS fed mice showed greater A2 expression and adipocyte size and reduced expression of PGC-1α, PPAR-γ, and adiponectin. A2 deletion blunted these effects, increased levels of active AMPK-α, and upregulated genes involved in fatty acid metabolism. A2 deletion prevented HFHS-induced VAT collagen deposition and inflammation, which are involved in adipocyte metabolic dysfunction. Endothelium-dependent vasorelaxation, impaired by HFHS diet, was significantly preserved in A2−/− mice, but more prominently maintained in A1+/− mice. In summary, A2 is critically involved in HFHS-induced VAT inflammation and metabolic dysfunction.

scholarly journals Increased Subcutaneous Adipose Tissue Expression of Genes Involved in Glycerolipid-Fatty Acid Cycling in Obese Insulin-Resistant Versus -Sensitive Individuals

2014 ◽  
Vol 99 (12) ◽  
pp. E2518-E2528 ◽  
Author(s):  
Marie-Soleil Gauthier ◽  
Joelle R. Pérusse ◽  
Marie-Ève Lavoie ◽  
Robert Sladek ◽  
S. R. Murthy Madiraju ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Subcutaneous Adipose Tissue ◽  
Tissue Expression ◽  
Insulin Resistant ◽  
Expression Of Genes ◽  
Subcutaneous Adipose

Fatty acid recycling in adipocytes: a role for glyceroneogenesis and phosphoenolpyruvate carboxykinase

2003 ◽  
Vol 31 (6) ◽  
pp. 1125-1129 ◽  
Author(s):  
C. Forest ◽  
J. Tordjman ◽  
M. Glorian ◽  
E. Duplus ◽  
G. Chauvet ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Amino Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
White Adipose Tissue ◽  
Metabolic Pathway ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Important Pathway ◽  
Low Activity

FA (fatty acid) recycling in adipose tissue appears to be an important pathway for regulating FA release into the blood during fasting. Re-esterification requires G3P (glycerol 3-phosphate), which cannot be synthesized from glucose because glycolysis is much reduced under such circumstances. In addition, G3P can scarcely originate from glycerol since glycerol kinase has a very low activity in white adipose tissue. It was shown about 35 years ago that a metabolic pathway named glyceroneogenesis, which allows G3P synthesis from non-carbohydrate precursors like pyruvate, lactate or amino acids, is activated during fasting. The major enzyme in this pathway was shown to be PEPCK-C [cytosolic phosphoenolpyruvate carboxykinase (GTP); EC 4.1.1.32]. The present review analyses the mechanisms by which a series of hormones and nutrients affect PEPCK-C gene transcription and glyceroneogenesis and describes evidence for dysregulation of this pathway in type 2 diabetes.

scholarly journals The Beige Adipocyte as a Therapy for Metabolic Diseases

2019 ◽  
Vol 20 (20) ◽  
pp. 5058 ◽  
Author(s):  
Fernando Lizcano
Keyword(s):  
Diabetes Mellitus ◽  
Adipose Tissue ◽  
Diabetes Mellitus Type 2 ◽  
Metabolic Diseases ◽  
Brown Fat ◽  
Diabetes Mellitus Type ◽  
Beige Adipocyte ◽  
Obesity And Diabetes ◽  
Beige Adipocytes

Adipose tissue is traditionally categorized into white and brown relating to their function and morphology. The classical white adipose tissue builds up energy in the form of triglycerides and is useful for preventing fatigue during periods of low caloric intake and the brown adipose tissue more energetically active, with a greater number of mitochondria and energy production in the form of heat. Since adult humans possess significant amounts of active brown fat depots and its mass inversely correlates with adiposity, brown fat might play an important role in human obesity and energy homeostasis. New evidence suggests two types of thermogenic adipocytes with distinct developmental and anatomical features: classical brown adipocytes and beige adipocytes. Beige adipocyte has recently attracted special interest because of its ability to dissipate energy and the possible ability to differentiate themselves from white adipocytes. The presence of brown and beige adipocyte in human adults has acquired attention as a possible therapeutic intervention for metabolic diseases. Importantly, adult human brown appears to be mainly composed of beige-like adipocytes, making this cell type an attractive therapeutic target for obesity and obesity-related diseases, such as atherosclerosis, arterial hypertension and diabetes mellitus type 2. Because many epigenetics changes can affect beige adipocyte differentiation from adipose progenitor cells, the knowledge of the circumstances that affect the development of beige adipocyte cells may be important to new pathways in the treatment of metabolic diseases. New molecules have emerged as possible therapeutic targets, which through the impulse to develop beige adipocytes can be useful for clinical studies. In this review will discuss some recent observations arising from the unique physiological capacity of these cells and their possible role as ways to treat obesity and diabetes mellitus type 2.

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