Ription factor is a crucial mediator on the cellular stress response and has been implicated in many nutrient-regulated processes.eight FoxO1 modulates lipid metabolism in AT by means of regulation of adipocyte size and the expression of AT-specific gene for example adipose triglyceride lipase (ATGL), the rate-limiting enzyme involved inside the breakdown of TG stored into LDs.9 An alternative technique to obtain FFAs from LDs has been firstly found in hepatocytes, which consists in LDs breakdown by way of autophagy by lysosomal lipases.10 This selective autophagy, named lipophagy, has been observed also in other cells including fibroblasts,11 neurons12 and even cancer cells,13 suggesting a generalized function of autophagy in cellular lipid mobilization. It has been demonstrated that intracellular lipid mobilization is cIAP1 drug particularly advantageous throughout NR, and lipophagy-mediated FFAs liberation essentially serves to keep cellular energy homeostasis.ten,14 In AT, the part of autophagy continues to be controversial. Certainly, it regulates AT improvement, being vital for adipocytes1 ` Division of Biology, University of Rome Tor Vergata, By means of della Ricerca Scientifica, Rome 00133, Italy; 2Universita Telematica di Roma San Raffaele, Via di Val Cannuta, Rome 00166, Italy and 3IRCCS San Raffaele, Biochemistry of Ageing, By means of di Val Cannuta, Rome 00166, Italy Corresponding author: K Aquilano, Division of Biology, University of Rome Tor Vergata, By means of della Ricerca Scientifica, Rome 00133, Italy. Tel: +39 06 7259 4312, Fax: +39 06 7259 4311; Thymidylate Synthase drug E-mail: [email protected] or MR Ciriolo, Department of Biology, University of Rome Tor Vergata, Through della Ricerca Scientifica, Rome, 00133, Italy. Tel: +39 06 7259 4369; Fax: +39 06 7259 4311; E-mail: [email protected] Keyword phrases: aging; ATGL; lipid metabolism; adipose tissue; autophagy Abbreviations: ATGL, adipose triglyceride lipase; Lipa, lysosomal acid lipase; FoxO1, forkhead homeobox form protein O1; EGFP, enhanced green fluorescent protein; TG, triglycerides; FFAs, cost-free fatty acids; NR, nutrient restriction; Metf, metformin; AT, adipose tissue; ORO, Oil Red-O; LDs, lipid dropletsReceived 29.7.13; revised 11.9.13; accepted 13.9.13; Edited by G MelinoNR and metformin induce lipophagy in adipocytes D Lettieri Barbato et aldifferentiation.15 Accordingly, increased autophagy in AT has been related with obesity and type-2 diabetes in mice and humans.16,17 A lot more lately, autophagy has been implicated in LDs degradation in fat cells both under basal and hormonestimulated lipolysis,18 thus implicating it in FFAs release from AT and possibly fat mass decrease. It can be now clearly evident that an imbalance between the hydrolysis and synthesis of TG is involved in excessive fat pad accumulation and critical for the development of age-related metabolic problems. For this reason, the manipulation of lipid metabolism at pharmacological level represents an appealing approach to extend life and healthspan. Among the emerging antiaging drugs, metformin (Metf) is incorporated.191 It truly is presently utilized as an oral antidiabetic specifically in overweight and obese subjects.22 Besides the well-recognized hypoglycemizing action, due to its capability to raise peripheral glucose uptake, Metf has been found to induce autophagy.23,24 Metf was shown to result in a mild energetic drop thus mimicking a NR-related state.19,25 Notwithstanding, the precise mechanisms behind the geroprotective effect of Metf are usually not nevertheless clearly established, element.