Activated AMP-activated protein kinase prevents hepatic steatosis, oxidative stress and inflammation in primary chicken hepatocytes

Abstract

Fatty liver hemorrhagic syndrome (FLHS) in laying hens, a nutritional metabolic disorder disease, can lead to the decline of laying rate, shortening of laying peak period and increase of mortality, which seriously constrain the sustainable development of layer industry. Until now, there is no effective strategies can prevent and control the occurrence of fatty liver hemorrhagic syndrome in laying hens. The AMP-activated protein kinase (AMPK), a major sensor of cellular energy status, acts a crucial role in regulating lipid metabolism, oxidative stress and inflammatory responses in body. However, the potential molecular mechanisms about AMP-activated protein kinase signal in controlling the occurrence of fatty liver hemorrhagic syndrome are remain unclear. In present study, we found that the phosphorylated AMP-activated protein kinase (Thr172) protein level was markedly reduced in palmitic acid plus oleic acid (PO)-induced primary chicken hepatocytes. Moreover, blocked AMP-activated protein kinase signal by AMP-activated protein kinase inhibitor compound C obviously exacerbated lipid metabolism disorders, oxidative stress and inflammatory response triggered by palmitic acid plus oleic acid in primary chicken hepatocytes. Nevertheless, the lipid metabolism disorders, oxidative stress and inflammatory response challenged by palmitic acid plus oleic acid were obviously alleviated through activation of AMP-activated protein kinase signal with AMP-activated protein kinase activator AICAR in hepatocytes. In addition, we found that the beneficial effects of AMP-activated protein kinase signal in relieving lipid metabolism disorders, oxidative stress and inflammatory response are achieved by activating the nuclear factor erythroid 2-related factor 2 (NRF-2)/kelch-like ECH-associated protein 1 (KEAP1) pathway and inhibiting the NF-κB pathway in PO-stimulated primary chicken hepatocytes. Collectively, our data demonstrated that AMP-activated protein kinase acts as a potential target for the prevention of fatty liver hemorrhagic syndrome occurrence in laying hens.

Osteocalcin and Its Potential Functions for Preventing Fatty Liver Hemorrhagic Syndrome in Poultry

“…In poultry, AMPK signaling pathway regulates the lipometabolism in FLHS chickens, enhancing fatty acid catabolism and restraining fatty acid anabolism [ 109 ]. Similar results have been demonstrated in other studies [ 107 ]. The AMPK signaling pathway, for example, is involved in the process of hepatic steatosis in laying hens [ 110 ].…”

“…AMPK is an important energy sensor that regulates metabolic homeostasis [ 106 ]. The activity of AMPK is inhibited in FLHS since up-regulated AMPK is beneficial in preventing the occurrence of related metabolic diseases by affecting lipometabolism, autophagy, and oxidative stress [ 107 , 108 ].…”

“…The AMPK signaling pathway, for example, is involved in the process of hepatic steatosis in laying hens [ 110 ]. Activation of AMPK reduces lipid synthesis-related genes and protein levels, thereby decreasing the lipid production in hepatocytes [ 107 , 110 ]. Fu et al [ 111 ] reported that maternally taking linoleic acid (CLA) supplementation mediates embryonic hepatic lipometabolism via the AMPK pathway.…”

“…Oleic acid (OA)-stimulation downregulates the Nrf-2 mRNA and nuclear protein levels in the primary chicken hepatocytes and LMH cells [ 121 ]. In addition, palmitic acid plus oleic acid (PO) treatment leads to markedly reduced nuclear Nrf-2 protein level, thus reducing the antioxidant capacity, which finally leads to a vicious circle of oxidative stress in the primary chicken hepatocytes [ 107 ]. Dysregulation of Nrf-2 may contribute to the developing of FLHS [ 121 ].Daily injection of ucOCN increases the nuclear Nrf-2 level in mice [ 73 ].…”

“…In addition, ucOCN may affect oxidative stress via the AMPK/ Nrf-2 signaling pathway. In primary chicken hepatocytes, AMPK prevents lipid metabolism disorders, oxidative stress, and inflammatory response through activation of Nrf-2 signaling pathway [ 107 ]. ucOCN may affect oxidative stress by regulating the ADPN/AMPK/Nrf-2 signaling pathway in chicken FLHS ( Figure 4 ).…”