Understanding the adipose tissue acetylome in obesity and insulin resistance

Abstract

Obesity is a widely prevalent pathology with a high exponential growth worldwide. Altered lipid accumulation by adipose tissue is one of the main causes of obesity and exploring lipid homeostasis in this tissue may represent a source for the identification of possible therapeutic targets. The study of the proteome and the post-translational modifications of proteins, specifically acetylation due to its involvement in energy metabolism, may be of great interest to understand the molecular mechanisms involved in adipose tissue dysfunction in obesity. The objective of this study was to characterize the subcutaneous and omental adipose tissue acetylome in conditions of obesity and insulin resistance and to describe the importance of acetylation of key molecules in adipose tissue to use them as therapeutic targets. The results describe for the first time the acetylome of subcutaneous and omental adipose tissue under physiological and physiopathological conditions such as obesity and insulin resistance. New evidence showed different acetylation patterns between two main depots and highlight the molecular complexity of adipose tissue. Results showed changes in FABP4 acetylation in subcutaneous fat in relation to insulin resistance, thus unveiling a potential marker of depot-specific dysfunctional expansion in obesity-associated metabolic disease. Furthermore, it is shown that the acetylation of FABP4 affects its function, modulating the capacity of differentiation in adipocytes. In conclusion, this study demonstrates a profound, depot-specific alteration of adipose tissue acetylome, wherein the acetylation of FABP4 may play a key role in adipocyte differentiation and lipid accumulation. Obesity is a widely prevalent pathology with a high exponential growth worldwide. Altered lipid accumulation by adipose tissue is one of the main causes of obesity and exploring lipid homeostasis in this tissue may represent a source for the identification of possible therapeutic targets. The study of the proteome and the post-translational modifications of proteins, specifically acetylation due to its involvement in energy metabolism, may be of great interest to understand the molecular mechanisms involved in adipose tissue dysfunction in obesity. The objective of this study was to characterize the subcutaneous and omental adipose tissue acetylome in conditions of obesity and insulin resistance and to describe the importance of acetylation of key molecules in adipose tissue to use them as therapeutic targets. The results describe for the first time the acetylome of subcutaneous and omental adipose tissue under physiological and physiopathological conditions such as obesity and insulin resistance. New evidence showed different acetylation patterns between two main depots and highlight the molecular complexity of adipose tissue. Results showed changes in FABP4 acetylation in subcutaneous fat in relation to insulin resistance, thus unveiling a potential marker of depot-specific dysfunctional expansion in obesity-associated metabolic disease. Furthermore, it is shown that the acetylation of FABP4 affects its function, modulating the capacity of differentiation in adipocytes. In conclusion, this study demonstrates a profound, depot-specific alteration of adipose tissue acetylome, wherein the acetylation of FABP4 may play a key role in adipocyte differentiation and lipid accumulation. At A Glance CommentaryM. Carmen Navarro-Ruiz, et al.BackgroundObesity is a complex disease that requires a maximum understanding of the biology of adipose tissue, the main organ affected in this pathology, to develop effective therapies.Translational SignificanceTherefore, analysing processes that modulate the functionality of adipose tissue to store fat and manage excess energy is essential for the treatment of obesity and its comorbidities. In this line, the acetylation of proteins, that controls energy metabolism in other tissues, could be a key component in the physio(patho)logy of adipose tissue which has not yet been described.INTRODUCTIONObesity is a chronic pathology, which constantly grown worldwide during the last decades, being one of the main causes of death in the world. Moreover, it is often an independent risk factor of insulin resistance (IR) and types 2 diabetes (T2D). Therefore, it is critical to understand the mechanism involved in the triggering of insulin resistance and type 2 diabetes associated with obesity, to discover new molecularly targeted treatments. Adipose tissue (AT) plays an essential role in obesity and excess energy storage, and its subsequent release as the production of signaling molecules secreted by adipocytes that exert functions on other cells, namely adipokines.1Unamuno X Gómez-Ambrosi J Rodríguez A Becerril S Frühbeck G Catalán V. Adipokine dysregulation and adipose tissue inflammation in human obesity.Eur J Clin Invest. 2018; 48: 0-2https://doi.org/10.1111/eci.12997Crossref Scopus (225) of biology to the of the for obesity metabolic not with and for risk X Gómez-Ambrosi J Rodríguez A Becerril S Frühbeck G Catalán V. Adipokine dysregulation and adipose tissue inflammation in human obesity.Eur J Clin Invest. 2018; 48: 0-2https://doi.org/10.1111/eci.12997Crossref Scopus (225) Moreover, it is that adipose tissue depot-specific of which to capacity for S Adipose tissue fat depots to Scopus of to adipose tissue expansion in Clin Invest. Scopus omental adipose tissue accumulation is associated with insulin resistance, subcutaneous fat expansion to be of to adipose tissue expansion in Clin Invest. Scopus the molecular mechanisms not yet The identification of depot-specific lipid metabolism that could as may the of obesity and metabolic which the identification of new has been to understand the complex biology obesity and its comorbidities. 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Carmen Navarro-Ruiz, et al.BackgroundObesity is a complex disease that requires a maximum understanding of the biology of adipose tissue, the main organ affected in this pathology, to develop effective therapies.Translational SignificanceTherefore, analysing processes that modulate the functionality of adipose tissue to store fat and manage excess energy is essential for the treatment of obesity and its comorbidities. In this line, the acetylation of proteins, that controls energy metabolism in other tissues, could be a key component in the physio(patho)logy of adipose tissue which has not yet been Carmen Navarro-Ruiz, et al.BackgroundObesity is a complex disease that requires a maximum understanding of the biology of adipose tissue, the main organ affected in this pathology, to develop effective therapies.Translational SignificanceTherefore, analysing processes that modulate the functionality of adipose tissue to store fat and manage excess energy is essential for the treatment of obesity and its comorbidities. In this line, the acetylation of proteins, that controls energy metabolism in other tissues, could be a key component in the physio(patho)logy of adipose tissue which has not yet been Carmen Navarro-Ruiz, et is a complex disease that requires a maximum understanding of the biology of adipose tissue, the main organ affected in this pathology, to develop effective Obesity is a complex disease that requires a maximum understanding of the biology of adipose tissue, the main organ affected in this pathology, to develop effective SignificanceTherefore, analysing processes that modulate the functionality of adipose tissue to store fat and manage excess energy is essential for the treatment of obesity and its comorbidities. In this line, the acetylation of proteins, that controls energy metabolism in other tissues, could be a key component in the physio(patho)logy of adipose tissue which has not yet been Therefore, analysing processes that modulate the functionality of adipose tissue to store fat and manage excess energy is essential for the treatment of obesity and its comorbidities. In this line, the acetylation of proteins, that controls energy metabolism in other tissues, could be a key component in the physio(patho)logy of adipose tissue which has not yet been is a chronic pathology, which constantly grown worldwide during the last decades, being one of the main causes of death in the world. Moreover, it is often an independent risk factor of insulin resistance (IR) and types 2 diabetes (T2D). Therefore, it is critical to understand the mechanism involved in the triggering of insulin resistance and type 2 diabetes associated with obesity, to discover new molecularly targeted treatments. Adipose tissue (AT) plays an essential role in obesity and excess energy storage, and its subsequent release as the production of signaling molecules secreted by adipocytes that exert functions on other cells, namely adipokines.1Unamuno X Gómez-Ambrosi J Rodríguez A Becerril S Frühbeck G Catalán V. Adipokine dysregulation and adipose tissue inflammation in human obesity.Eur J Clin Invest. 2018; 48: 0-2https://doi.org/10.1111/eci.12997Crossref Scopus (225) of biology to the of the for obesity metabolic not with and for risk X Gómez-Ambrosi J Rodríguez A Becerril S Frühbeck G Catalán V. Adipokine dysregulation and adipose tissue inflammation in human obesity.Eur J Clin Invest. 2018; 48: 0-2https://doi.org/10.1111/eci.12997Crossref Scopus (225) Moreover, it is that adipose tissue depot-specific of which to capacity for S Adipose tissue fat depots to Scopus of to adipose tissue expansion in Clin Invest. Scopus omental adipose tissue accumulation is associated with insulin resistance, subcutaneous fat expansion to be of to adipose tissue expansion in Clin Invest. Scopus the molecular mechanisms not yet The identification of depot-specific lipid metabolism that could as may the of obesity and metabolic which the identification of new has been to understand the complex biology obesity and its comorbidities. In to and the of the proteome the of post-translational modifications and A in and for Scopus acetylation is one of the and has for its role in the of key that energy acetylation on which is of and A The of Scopus of the of the metabolism to be in different A of and energy metabolism in obesity, and Scopus et role of acetylation in and metabolism to Scopus J et acetylome study of human for and therapeutic Scopus In adipose tissue, in and in the importance of acetylation of for adipocyte differentiation under et of adipocyte differentiation and Scopus and conditions obesity, A The of Scopus A acetylation in obesity, diabetes and metabolic Scopus involved in functions in the is a lipid that in the of it is an functions of and therapeutic Scopus in and metabolic Scopus Moreover, different such as has been for which may its and for of Scopus J Adipokine FABP4 energy and metabolic Scopus of acetylation during adipocyte Scopus has been by in and the of such to be J Adipokine FABP4 energy and metabolic Scopus describe for the first an proteome of subcutaneous and omental during the of obesity and insulin resistance. the study acetylation in the adipose tissue as a potential between obesity and in subcutaneous and the of acetylation as a key of proteins, such as to understand the complex role of in obesity and

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