Adiponectin Exerts Peripheral Inhibitory Effects on the Mouse Gastric Smooth Muscle through the AMPK Pathway

Abstract

Some adipokines, such as adiponectin (ADPN), other than being implicated in the central regulation of feeding behavior, may influence gastric motor responses, which are a source of peripheral signals that also influence food intake. The present study aims to elucidate the signaling pathways through which ADPN exerts its actions in the mouse gastric fundus. To this purpose, we used a multidisciplinary approach. The mechanical results showed that ADPN caused a decay of the strip basal tension, which was abolished by the nitric oxide (NO) synthesis inhibitor, L-NG-nitro arginine (L-NNA). The electrophysiological experiments confirmed that all ADPN effects were abolished by L-NNA, except for the reduction of Ca2+ current, which was instead prevented by the inhibitor of AMP-activated protein kinase (AMPK), dorsomorphin. The activation of the AMPK signaling by ADPN was confirmed by immunofluorescence analysis, which also revealed the ADPN R1 receptor (AdipoR1) expression in glial cells of the myenteric plexus. In conclusion, our results indicate that ADPN exerts an inhibitory action on the gastric smooth muscle by acting on AdipoR1 and involving the AMPK signaling pathway at the peripheral level. These findings provide novel bases for considering AMPK as a possible pharmacologic target for the potential treatment of obesity and eating disorders.

Evidence that resistin acts on the mechanical responses of the mouse gastric fundus

“…NO is considered as the major inhibitory neurotransmitter released from non-adrenergic, non-cholinergic (NANC) fibers supplying the smooth muscle and responsible for proximal stomach relaxation in both humans and rodents (Rand, 1992;Min et al, 2016;Idrizaj et al, 2021). In this view, we previously observed that a NO-dependent mechanism was implicated in the inhibitory actions of adiponectin on gastric smooth muscle activity (Idrizaj et al, 2018a;Idrizaj et al, 2019a;Idrizaj et al, 2020a). Interestingly, NO production has been shown to be also influenced by resistin in human vascular endothelial cells (Chen et al, 2010).…”

S1P Signalling Axis Is Necessary for Adiponectin-Directed Regulation of Electrophysiological Properties and Oxidative Metabolism in C2C12 Myotubes

“…Beside its effects on energy homeostasis, globular Adn has been shown to induce skeletal muscle differentiation of C2C12 murine myoblasts through a redox-dependent circuitry involving p38, Akt and AMPK signalling [ 13 ]. Moreover, Adn has been proven to cause alterations of the resting membrane potential and membrane electrophysiological properties as well as of K + and Ca 2+ currents, inhibiting smooth muscle contractility of the gastric fundus [ 14 ].…”

The Controversial Role of Adiponectin in Appetite Regulation of Animals

“…Recently, Idrizaj et al combined mechanical and electrophysiological methods, which further demonstrated that the effect of AdipoQ on K + or Ca 2+ current in SMCs was blocked in the presence of AMPK inhibitor (dorsomorphin). Meanwhile, western blotting analysis revealed that AdipoQ administration promoted the expression of phosphoAMPK (pAMPK) [95]. In addition, AdipoR1 was expressed by glial cells in the myenteric plexus, which was in keeping with the involvement of the AMPK pathway.…”