Transcriptional Dysregulation of Adipose Tissue Autophagy in Obesity

Maixner, Nitzan; Bechor, Sapir; Vershinin, Zlata; Pecht, Tal; Goldstein, Nir; Haim, Yulia; Rudich, Assaf

doi:10.1152/physiol.00048.2015

Cited by 34 publications

(34 citation statements)

References 75 publications

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“…4,5 In adipose tissue, how autophagy is dys-regulated remains unsettled, with a general agreement that autophagy genes are overexpressed in adipose tissue, particularly in depots and in obesity sub-types that are more associated with metabolic dysfunction. [6][7][8] Yet, although autophagy, particularly in chronic diseases, may be regulated also at the gene expression level, 9,10 much more is known about its more rapid regulation by post-translational modifications and proteinprotein interactions. Indeed, while two independent groups suggested that autophagic activity (i.e., 'flux') is inhibited in adipose tissue, 11,12 at least four groups, including our own, provided evidence that the elevated gene expression of autophagy genes in adipose tissue manifests by increased autophagic flux.…”

Section: Introductionmentioning

confidence: 99%

Leptin stimulates autophagy/lysosome-related degradation of long-lived proteins in adipocytes

et al. 2019

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Obesity, a condition most commonly associated with hyper-leptinemia, is also characterized by increased expression of autophagy genes and likely autophagic activity in human adipose tissue (AT). Indeed, circulating leptin levels were previously shown to positively associate with the expression levels of autophagy genes such as Autophagy related gene-5 (ATG5). Here we hypothesized that leptin acts in an autocrine-paracrine manner to increase autophagy in two major AT cell populations, adipocytes and macrophages. We followed the dynamics of autophagosomes following acute leptin administration with or without a leptin receptor antagonist (SMLA) using high-throughput live-cell imaging in murine epididymal adipocyte and macrophage (RAW264.7) cell-lines. In macrophages leptin exerted only a mild effect on autophagy dynamics, tending to attenuate autophagosomes growth rate. In contrast, leptin-treated adipocytes exhibited a moderate, ~20% increase in the rate of autophagosome growth, an effect that was blocked by SMLA. This finding corresponded to mild increases in mRNA and protein expression of key autophagy genes. Interestingly, a long-lived proteins degradation assay uncovered a robust, >2-fold leptin-mediated stimulation of the autophagy/lysosome-related (bafilomycin-inhibited) activity, which was entirely blocked by SMLA. Collectively, leptin regulates autophagy in a cell-type specific manner. In adipocytes, autophagosome dynamics is moderately enhanced, but even more pronounced stimulation is seen in autophagy-related long-lived protein degradation. These findings suggest a causal link between obesity-associated hyperleptinemia and elevated adipocyte and AT autophagy-related processes.

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Section: Introductionmentioning

confidence: 99%

Leptin stimulates autophagy/lysosome-related degradation of long-lived proteins in adipocytes

et al. 2019

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“…The previous studies had shown that an increased transcription of autophagy-related genes and proteins is associated with a dysfunction of adipose tissues and a higher risk of the development of cardiometabolic diseases. (7,9) If this is the case, the LCD28 group, which demonstrated autophagic activities, had a higher risk for cardiometabolic diseases compared to the other groups and control.…”

Section: Discussionmentioning

confidence: 96%

“…(6) Adipocyte hypertrophy especially in visceral adipose tissues which found in obesity could induce autophagy. (7)(8)(9)(10) Autophagy is a lysosomal degradation pathway in which organelles and other components of the cell are compartmentalized within a doublemembran vesicle, the autophagosome, and undergoing degradation by lysosomal enzymes and recycled. It is essential for survival, differentiation, development, and cell homeostasis.…”

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confidence: 99%

Hypoxia and autophagic response of obese adult rat adipocytes which differ in nutritional state during childhood

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Jusuf

Jusman

et al. 2020

J. Clin. Biochem. Nutr.

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The prevalence of obesity in adults is increasing worldwide, which is problematic since obesity is associated with degenerative diseases. Nowadays Indonesia is facing an interesting phenomenon since there are adults who have been obese since childhood and others who conversely were undernourished while young. The biological differences of these two types of obesities are not well understood. This study aims to analyse the difference in the size and number of visceral adipocytes, HIF 1α, HIF 2α and MAP1LC3A/ LC3 in obese adult rat groups that were undernourished at a young age compared to groups who were normal or even already fat from childhood. We analyzed Hif 1α, Hif 2α, Lc3 mRNA by RT qPCR; HIF 1α, HIF 2α, MAP1LC3A/LC3 protein level by ELISA. The HIF 1α and HIF 2α protein level of visceral adipocytes derived from the group of rat which were undernourished while young increased significantly compared to the group which was overnourished. The visceral adipocytes of the group which was overnourished since childhood showed an increase in Hif 2α mRNA level. The Lc3 mRNA of the rat group which were undernourished since young increased significantly compared to rat group which was obese since childhood.

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“…To date, autophagy in ASCs represents a relevant topic. It significantly contributes to the dysregulation of the adipose tissue by controlling lipid accumulation, and balancing white and brown fat deposition (Singh et al, 2009;Maixner et al, 2016). Intriguingly, autophagy is enhanced in obesity and associated to visceral fat distribution (Kovsan et al, 2011), thus encouraging further investigations on the ability of the stromal subset during adipogenic commitment.…”

Section: Discussionmentioning

confidence: 99%

The adipose tissue of origin influences the biological potential of human adipose stromal cells isolated from mediastinal and subcutaneous fat depots

et al. 2016

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Indirect evidence suggests that adipose tissue-derived stromal cells (ASCs) possess different physiological and biological variations related to the anatomical localization of the adipose depots. Accordingly, to investigate the influence of the tissue origin on the intrinsic properties of ASCs and to assess their response to specific stimuli, we compared the biological, functional and ultrastructural properties of two ASC pools derived from mediastinal and subcutaneous depots (thoracic compartment) by means of supplements such as platelet lysate (PL) and FBS. Subcutaneous ASCs exhibited higher proliferative and clonogenic abilities than mediastinal counterpart, as well as increased secreted levels of IL-6 combined with lower amount of VEGF-C. In contrast, mediastinal ASCs displayed enhanced pro-angiogenic and adipogenic differentiation properties, increased cell diameter and early autophagic processes, highlighted by electron microscopy. Our results further support the hypothesis that the origin of adipose tissue significantly defines the biological properties of ASCs, and that a homogeneric function for all ASCs cannot be assumed.

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Transcriptional Dysregulation of Adipose Tissue Autophagy in Obesity

Cited by 34 publications

References 75 publications

Leptin stimulates autophagy/lysosome-related degradation of long-lived proteins in adipocytes

Leptin stimulates autophagy/lysosome-related degradation of long-lived proteins in adipocytes

Hypoxia and autophagic response of obese adult rat adipocytes which differ in nutritional state during childhood

The adipose tissue of origin influences the biological potential of human adipose stromal cells isolated from mediastinal and subcutaneous fat depots

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