Diet-induced obesity affects expression of adiponutrin/PNPLA3 and adipose triglyceride lipase, two members of the same family

Oliver, Paula; Caimari, Antoni; Díaz‐Rúa, Rubén; Palou, Andreu

doi:10.1038/ijo.2011.92

Cited by 24 publications

(20 citation statements)

References 45 publications

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“…Of note, expression of both enzymes was reported to be decreased in adipose tissue in obesity, thus leaving a possibility that downregulation of Atgl and Hsl transcript levels in Clock Δ19 and Bmal1 −/− animals might be rather the consequence than the cause of their adiposity. Our in vitro data suggest that Atgl and Hsl are direct targets of CLOCK/BMAL1, independent of metabolic state, but further studies are needed to clarify the impact of body weight and composition in this context (43,44). Moreover, we cannot exclude that disrupted feeding rhythms in Clock Δ19 (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 89%

Circadian Regulation of Lipid Mobilization in White Adipose Tissues

2013

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In mammals, a network of circadian clocks regulates 24-h rhythms of behavior and physiology. Circadian disruption promotes obesity and the development of obesity-associated disorders, but it remains unclear to which extent peripheral tissue clocks contribute to this effect. To reveal the impact of the circadian timing system on lipid metabolism, blood and adipose tissue samples from wild-type, ClockΔ19, and Bmal1−/− circadian mutant mice were subjected to biochemical assays and gene expression profiling. We show diurnal variations in lipolysis rates and release of free fatty acids (FFAs) and glycerol into the blood correlating with rhythmic regulation of two genes encoding the lipolysis pacemaker enzymes, adipose triglyceride (TG) lipase and hormone-sensitive lipase, by self-sustained adipocyte clocks. Circadian clock mutant mice show low and nonrhythmic FFA and glycerol blood content together with decreased lipolysis rates and increased sensitivity to fasting. Instead circadian clock disruption promotes the accumulation of TGs in white adipose tissue (WAT), leading to increased adiposity and adipocyte hypertrophy. In summary, circadian modulation of lipolysis rates regulates the availability of lipid-derived energy during the day, suggesting a role for WAT clocks in the regulation of energy homeostasis.

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Section: Discussionmentioning

confidence: 89%

Circadian Regulation of Lipid Mobilization in White Adipose Tissues

2013

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“…Fortunately, fasting plasma FA levels demonstrate a much more modest increase and are largely unrelated to body fat mass (48), although the mechanisms of this compensation are not known. One such mechanism may be the suppression of ATGL expression (32,49) by Egr1 and FSP27 that are both up-regulated by high fat feeding (32,50). This may represent a compensatory response in adipocytes that keeps circulating FA within physiological range and protects the body from detrimental effects of obesity.…”

Section: Resultsmentioning

confidence: 99%

Fat-specific Protein 27 Inhibits Lipolysis by Facilitating the Inhibitory Effect of Transcription Factor Egr1 on Transcription of Adipose Triglyceride Lipase

Singh

Kaur

Lee

et al. 2014

Journal of Biological Chemistry

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Background: FSP27 is a lipid droplet-associated protein.Results: Expression of FSP27 in human adipocytes reversely correlates with ATGL levels. Mechanistically, FSP27 increases the inhibitory effect of Egr1 on the ATGL promoter. Conclusion: FSP27 controls lipolysis by regulating ATGL transcription. Significance: Our study provides a new model of regulation of lipolysis in adipocytes. Current epidemics of metabolic diseases, such as type 2 diabetes, cardiac dysfunction, hypertension, hepatic steatosis, etc., are largely caused by widespread obesity. Although obesity can affect human health via several different mechanisms (1), the best established connection between obesity and metabolic disease is abnormal levels of circulating fatty acids (FA). 3 FA play important physiological roles in energy production and the synthesis of most lipids; nonetheless, their oversupply is highly detrimental as it leads to insulin resistance, oxidative stress, and other pathophysiological effects via mechanisms that are currently under intense investigation (1-5). Lipolysis in fat tissueNormally, dietary FA are partitioned into adipose tissue, converted into triglycerides, and stored in lipid droplets (LDs) that represent dynamic intracellular organelles consisting of a core of triglycerides and cholesterol esters, surrounded by a monolayer of phospholipids. Several proteins are associated with this monolayer, notably the PAT family proteins, PLIN 1-5 (6, 7), and fat-specific protein 27 (FSP27, also known as CIDEC) (8 -10). The latter protein plays an essential role in the regulation of LD morphology. Depletion of FSP27 in adipocytes leads to fragmentation of LDs (11,12), whereas overexpression of FSP27 increases the size of LDs while decreasing their number (8, 9, 12) by promoting LD fusion (13) and exchanging lipids from one droplet to another (14).It has also been demonstrated by us and others that FSP27 has anti-lipolytic activity (8,9,12,(15)(16)(17)(18). Lipolysis in adipose tissue is the major source of circulating . Correspondingly, unrestricted lipolysis in adipose tissue represents a serious metabolic defect and a causative factor of insulin resistance, diabetes mellitus, and other metabolic diseases (3,(25)(26)(27). As the mechanism of the anti-lipolytic activity of FSP27 is not completely clear, we decided to focus on this problem.Our recent study showed that FSP27 directly interacts with ATGL and regulates its lipase activity (18). Another study predicted that FSP27-mediated fusion of LDs might limit the access of intracellular lipases to the LD surface due to decreased surface area of larger LDs (17). As ATGL represents a major lipolytic enzyme (28), reducing its contact with LDs may suppress lipolysis.Here, we report another mechanism of the anti-lipolytic action of FSP27 in human adipocytes. We have found that FSP27 inhibits expression of ATGL at the level of transcription by stimulating the effect of its transcriptional repressor Egr1. EXPERIMENTAL PROCEDURESCell Culture-Human preadipocytes were procured from the ...

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“…PNPLA3 has a target site for miR-30a. PNPLA3 is upregulated in adipose tissue of obese mice and its expression is regulated by changes in the energy balance in humans [46,47]. IL-6 is a pro-inflammatory cytokine that regulates lipid metabolism in adipose tissue and plasma IL-6 levels correlates with BMI in humans [48,49].…”

Section: Discussionmentioning

confidence: 99%

Joint Profiling of miRNAs and mRNAs Reveals miRNA Mediated Gene Regulation in the Göttingen Minipig Obesity Model

et al. 2016

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Obesity and its comorbidities are an increasing challenge for both affected individuals and health care systems, worldwide. In obese individuals, perturbation of expression of both protein-coding genes and microRNAs (miRNA) are seen in obesity-relevant tissues (i.e. adipose tissue, liver and skeletal muscle). miRNAs are small non-coding RNA molecules which have important regulatory roles in a wide range of biological processes, including obesity. Rodents are widely used animal models for human diseases including obesity. However, not all research is applicable for human health or diseases. In contrast, pigs are emerging as an excellent animal model for obesity studies, due to their similarities in their metabolism, their digestive tract and their genetics, when compared to humans. The Göttingen minipig is a small sized easy-to-handle pig breed which has been extensively used for modeling human obesity, due to its capacity to develop severe obesity when fed ad libitum. The aim of this study was to identify differentially expressed of protein-coding genes and miRNAs in a Göttingen minipig obesity model. Liver, skeletal muscle and abdominal adipose tissue were sampled from 7 lean and 7 obese minipigs. Differential gene expression was investigated using high-throughput quantitative real-time PCR (qPCR) on 90 mRNAs and 72 miRNAs. The results revealed de-regulation of several obesity and inflammation-relevant protein-coding genes and miRNAs in all tissues examined. Many genes that are known to be de-regulated in obese humans were confirmed in the obese minipigs and several of these genes have target sites for miRNAs expressed in the opposing direction of the gene, confirming miRNA-mediated regulation in obesity. These results confirm the translational value of the pig for human obesity studies.

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Diet-induced obesity affects expression of adiponutrin/PNPLA3 and adipose triglyceride lipase, two members of the same family

Cited by 24 publications

References 45 publications

Circadian Regulation of Lipid Mobilization in White Adipose Tissues

Circadian Regulation of Lipid Mobilization in White Adipose Tissues

Fat-specific Protein 27 Inhibits Lipolysis by Facilitating the Inhibitory Effect of Transcription Factor Egr1 on Transcription of Adipose Triglyceride Lipase

Joint Profiling of miRNAs and mRNAs Reveals miRNA Mediated Gene Regulation in the Göttingen Minipig Obesity Model

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