Abstract
Adiponectin (ApN) is a hormone abundantly secreted by adipocytes and it is known to be tightly linked to the metabolic syndrome. It promotes insulin-sensitizing, fat-burning, and anti-atherosclerotic actions, thereby effectively counteracting several metabolic disorders, including type 2 diabetes, obesity, and cardiovascular diseases. ApN is also known today to possess powerful anti-inflammatory/oxidative and pro-myogenic effects on skeletal muscles exposed to acute or chronic inflammation and injury, mainly through AdipoR1 (ApN specific muscle receptor) and AMP-activated protein kinase (AMPK) pathway, but also via T-cadherin. In this review, we will report all the beneficial and protective properties that ApN can exert, specifically on the skeletal muscle as a target tissue. We will highlight its effects and mechanisms of action, first in healthy skeletal muscle including exercised muscle, and second in diseased muscle from a variety of pathological conditions. In the end, we will go over some of AdipoRs agonists that can be easily produced and administered, and which can greatly mimic ApN. These interesting and newly identified molecules could pave the way towards future therapeutic approaches to potentially prevent or combat not only skeletal muscle disorders but also a plethora of other diseases with sterile inflammation or metabolic dysfunction.
Highlights
Adiponectin (ApN) is a hormone abundantly secreted by adipocytes; it is found in plasma at high concentrations (~ μg/mL; at least 3 orders of magnitude higher than other hormones)
PGC-1α increases the activity of several transcriptions factors (TF), stimulating the expression of target genes leading to an increase of mitochondrial biogenesis and a shift towards an oxidative metabolism [11] (Figure 2)
We previously showed that muscles of ApN-deficient mice displayed higher susceptibility to oxidative stress, inflammation, and apoptosis; all these abnormalities were exacerbated by acute (LPS) or chronic inflammatory challenge and corrected by local electro-transfer of the ApN gene [39,40]
Summary
Adiponectin (ApN) is a hormone abundantly secreted by adipocytes; it is found in plasma at high concentrations (~ μg/mL; at least 3 orders of magnitude higher than other hormones). Plasma ApN levels are decreased in obesity and in patients meeting the criteria for the metabolic syndrome. HMW ApN elicits the most potent insulin-sensitizing effects [6]. MAdaiipnolyRe1xipsremssaeindlyinesxkperleestsaeldmiunscslkee, lwethalermeaussAcled,ipwohRe2reiassprAeddiopmoRin2anistlpyreexdpormesinseadntilny the livexepr r[e1s0s]e.dAidnipthoeRl1iviesrti[g1h0]t.lyAldinipkoeRd1toisatcigtihvtalytiolinnkoefdAtMo Pac-aticvtaivtiaotnedofpAroMtePin‐akctiinvaasteed(ApMroPteKin) pkainthasweays, w(hAiMlePAKd)ippaotRhw saeyesm, wshtiolebAedaispsooRc2iasteeedmws ittohbaecatisvsoactiioatnedofwpitehroaxctisivoamtieonporof lpifeerroaxtiosor-macetpivraotliefderraetocer‐ptor (PaPcAtivRa)t-eαdpraetchewptaoyrs(P[9P,A11R]).‐Aα dpiapthoRw1ayiss a[9h,1ig1]h.-AaffidinpiotRy1reisceaphtoigrhf‐oarffginAiptyNrebcuetpctoarnfaolrsogAbpinNd bfuultl-claenngth AaplsNo. bAinddipfuolRl‐2lenshgothwAspiNnt.eArmdiepdoiRa2teshaoffiwnsitiyntfeormr bedoitahtethafefigniltoybfuolrarboatnhdthteheglofublul-lalernagntdh tfhoermfusll‐[10]. ApN is able to regulate food intake, energy expenditure, and lipid and glucose metabolism by acting on the hypothalamus [27,28]. It exerts anti-depressive effects by increasing hippocampal neurogenesis and reducing neuroinflammation [29,30,31]. ApN could protect against cancer progression in most obesity-related cancer types, such as colorectal and breast cancers, through its abilities to induce apoptosis and to limit cell proliferation and angiogenesis [33]
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