Hints on ATGL implications in cancer: beyond bioenergetic clues

Abstract

Among metabolic rearrangements occurring in cancer cells, lipid metabolism alteration has become a hallmark, aimed at sustaining accelerated proliferation. In particular, fatty acids (FAs) are dramatically required by cancer cells as signalling molecules and membrane building blocks, beyond bioenergetics. Along with de novo biosynthesis, free FAs derive from dietary sources or from intracellular lipid droplets, which represent the storage of triacylglycerols (TAGs). Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme of lipolysis, catalysing the first step of intracellular TAGs hydrolysis in several tissues. However, the roles of ATGL in cancer are still neglected though a putative tumour suppressor function of ATGL has been envisaged, as its expression is frequently reduced in different human cancers (e.g., lung, muscle, and pancreas). In this review, we will introduce lipid metabolism focusing on ATGL functions and regulation in normal cell physiology providing also speculative perspectives on potential non-energetic functions of ATGL in cancer. In particular, we will discuss how ATGL is implicated, mainly through the peroxisome proliferator-activated receptor-α (PPAR-α) signalling, in inflammation, redox homoeostasis and autophagy, which are well-known processes deregulated during cancer formation and/or progression.

High Dietary Fat Intake Affects DNA Methylation/Hydroxymethylation in Mouse Heart: Epigenetic Hints for Obesity‐Related Cardiac Dysfunction

“…At this intermediate time point, the decrease of 5hmC was already appreciable while no 5fC staining was yet detected (Figure S1B, Supporting Information). As HFD treatment was able to increase fatty acid levels in heart tissue (Figure S1C, Supporting Information), we wondered whether the observed epigenetic alterations are also present in mice lacking the triglyceride lipase Atgl, which accumulate lipids in heart also in basal conditions and die for cardiomyopathy . However, the levels of 5hmC in hearts were comparable between wild‐type and Atgl knockout mice (Figure D).…”

“…As HFD treatment was able to increase fatty acid levels in heart tissue ( Figure S1C, Supporting Information), we wondered whether the observed epigenetic alterations are also present in mice lacking the triglyceride lipase Atgl, which accumulate lipids in heart also in basal conditions and die for cardiomyopathy. [16] However, the levels of 5hmC in hearts were comparable between wild-type and Atgl knockout mice ( Figure 1D). To determine whether the effects of HFD on DNA hydroxymethylation were systemic, dot-blot analysis was recapitulated in brain, the organ with the highest content of 5hmC, [17] but no consistent results were obtained ( Figure 1E).…”

Flavonoids as Anticancer Agents

“…The main metabolic alterations of the tumor cells involve increased aerobic glycolysis [42], deregulated pH [43], impaired lipid metabolism [44], increased generation of ROS [45], and compromised enzyme activities [38,46] (Figure 8). As a direct consequence, the extracellular environment becomes acidic and more favorable to inflammation [47], glutamine-driven lipid biosynthesis increases and upregulates the pathways involved in tumorigenesis initiation and metastasis [48], cardiolipin levels decrease in membranes causing impaired enzyme activities [49][50][51], mitochondria are hyperpolarised [38], and this effect correlates with the malignancy and invasiveness of cancer cells [38].…”

Accurate 3-gene-signature for early diagnosis of liposarcoma progression

“…This is a very relevant aspect for the possible implication of LIPE in the pathogenic mechanism, as retinoic acid (RA) pathway has well-established tumor suppressor function and its loss contributed to the loss of differentiation in WAT. Similarly, a recent review considers non-energetic tumorsuppressive functions of PNPLA2 in cancer [27].…”