Functional Proteomic Analysis of Lipases and Esterases in Cultured Human Adipocytes

Schicher, Maximilian; Morak, Maria; Birner‐Gruenberger, Ruth; Kayer, Heidemarie; Stojcic, Bojana; Rechberger, Gerald; Kollroser, Manfred; Hermetter, Albin

doi:10.1021/pr1005795

Cited by 15 publications

(5 citation statements)

References 61 publications

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“…This is consistent with the absence of a catalytic serine residue. In agreement with this, a hydrolase activity screen in adipocytes failed to identify ABHD15 [25].…”

Section: Resultssupporting

confidence: 57%

ABHD15 regulates adipose tissue lipolysis and hepatic lipid accumulation

Stöckli

Zadoorian

Cooke

et al. 2019

Molecular Metabolism

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Objective Insulin suppresses adipose tissue lipolysis after a meal, playing a key role in metabolic homeostasis. This is mediated via the kinase Akt and its substrate phosphodiesterase 3B (PDE3B). Once phosphorylated and activated, PDE3B hydrolyses cAMP leading to the inactivation of cAMP-dependent protein kinase (PKA) and suppression of lipolysis. However, several gaps have emerged in this model. Here we investigated the role of the PDE3B-interacting protein, α/β-hydrolase ABHD15 in this process. Methods Lipolysis, glucose uptake, and signaling were assessed in ABHD15 knock down and knock out adipocytes and fat explants in response to insulin and/or β-adrenergic receptor agonist. Glucose and fatty acid metabolism were determined in wild type and ABHD15 −/− littermate mice. Results Deletion of ABHD15 in adipocytes resulted in a significant defect in insulin-mediated suppression of lipolysis with no effect on insulin-mediated glucose uptake. ABHD15 played a role in suppressing PKA signaling as phosphorylation of the PKA substrate Perilipin-1 remained elevated in response to insulin upon ABHD15 deletion. ABHD15 −/− mice had normal glucose metabolism but defective fatty acid metabolism: plasma fatty acids were elevated upon fasting and in response to insulin, and this was accompanied by elevated liver triglycerides upon β-adrenergic receptor activation. This is likely due to hyperactive lipolysis as evident by the larger triglyceride depletion in brown adipose tissue in these mice. Finally, ABHD15 protein levels were reduced in adipocytes from mice fed a Western diet, further implicating this protein in metabolic homeostasis. Conclusions Collectively, ABHD15 regulates adipocyte lipolysis and liver lipid accumulation, providing novel therapeutic opportunities for modulating lipid homeostasis in disease.

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“…This is consistent with the absence of a catalytic serine residue. In agreement with this, a hydrolase activity screen in adipocytes failed to identify ABHD15 [25].…”

Section: Resultssupporting

confidence: 57%

ABHD15 regulates adipose tissue lipolysis and hepatic lipid accumulation

Stöckli

Zadoorian

Cooke

et al. 2019

Molecular Metabolism

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“…In contrast, ABPP is a powerful analytical method to detect and compare protein activities across proteomes. The use of ABPP in general is increasing rapidly, but few probes have been synthesized that demonstrate compatibility with 2D-Gel analysis (Schicher et al, 2010). The majority of standard fluorescent dyes behave poorly on 2D-gels because they alter protein pI, decrease solubility, and/or result in smearing.…”

Section: Resultsmentioning

confidence: 99%

Global Analysis of Viral Infection in an Archaeal Model System

Maaty¹,

Steffens²,

Heinemann³

et al. 2012

Front. Microbio.

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The origin and evolutionary relationship of viruses is poorly understood. This makes archaeal virus-host systems of particular interest because the hosts generally root near the base of phylogenetic trees, while some of the viruses have clear structural similarities to those that infect prokaryotic and eukaryotic cells. Despite the advantageous position for use in evolutionary studies, little is known about archaeal viruses or how they interact with their hosts, compared to viruses of bacteria and eukaryotes. In addition, many archaeal viruses have been isolated from extreme environments and present a unique opportunity for elucidating factors that are important for existence at the extremes. In this article we focus on virus-host interactions using a proteomics approach to study Sulfolobus Turreted Icosahedral Virus (STIV) infection of Sulfolobus solfataricus P2. Using cultures grown from the ATCC cell stock, a single cycle of STIV infection was sampled six times over a 72 h period. More than 700 proteins were identified throughout the course of the experiments. Seventy one host proteins were found to change their concentration by nearly twofold (p < 0.05) with 40 becoming more abundant and 31 less abundant. The modulated proteins represent 30 different cell pathways and 14 clusters of orthologous groups. 2D gel analysis showed that changes in post-translational modifications were a common feature of the affected proteins. The results from these studies showed that the prokaryotic antiviral adaptive immune system CRISPR-associated proteins (CAS proteins) were regulated in response to the virus infection. It was found that regulated proteins come from mRNAs with a shorter than average half-life. In addition, activity-based protein profiling (ABPP) profiling on 2D-gels showed caspase, hydrolase, and tyrosine phosphatase enzyme activity labeling at the protein isoform level. Together, this data provides a more detailed global view of archaeal cellular responses to viral infection, demonstrates the power of quantitative two-dimensional differential gel electrophoresis and ABPP using 2D gel compatible fluorescent dyes.

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“…Forner et al 137 Insenser et al 160 Lim et al 174 Schmelzle et al 55 Kru ¨ger et al 56 Primary cells Zhou et al 58 Rat WAT Noel et al 165 Tissue explants (rat) Xie et al 57 Barcelo-Batllori et al 138 Roche et al 166 Roca-Rivada et al 178 Lanne et al 126 Schicher et al 167…”

Section: Adipocyte Components Tissue Explants (Mouse) Total Cellular ...mentioning

confidence: 99%

Application of proteomics technology in adipocyte biology

Renes

Mariman

2013

Mol. BioSyst.

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Obesity and its associated complications have reached epidemic proportions in Western-type societies. Concomitantly, the obesity incidence in developing countries is increasing. One hallmark of obesity is the differentiation of pre-adipocytes into mature triglyceride-loaded adipocytes present in subcutaneous and visceral adipose tissue depots. This may ultimately lead to dysfunctional adipose tissue together with detrimental changes in the profiles of (pre-)adipocyte-secreted proteins, known as adipokines. Obesity-induced alterations in adipokine profiles contribute to the development of obesity-associated disorders. Consequently, the interest in the molecular events responsible for adipose tissue modifications during weight gain and weight loss as well as in the aetiology of obesity-associated disorders is growing. Molecular mechanisms involved in pre-adipocyte differentiation and alterations in adipokine profiles have been examined at the gene and protein level by high-throughput technologies. Independent proteomics studies have contributed significantly to further insight into adipocyte biology, particularly with respect to adipokine profiling. In this review novel findings obtained with adipo-proteomics studies are highlighted and the relevance of proteomics technologies to further understand molecular aspects of adipocyte biology is discussed.

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Functional Proteomic Analysis of Lipases and Esterases in Cultured Human Adipocytes

Cited by 15 publications

References 61 publications

ABHD15 regulates adipose tissue lipolysis and hepatic lipid accumulation

ABHD15 regulates adipose tissue lipolysis and hepatic lipid accumulation

Global Analysis of Viral Infection in an Archaeal Model System

Application of proteomics technology in adipocyte biology

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