Osteocalcin prevents insulin resistance, hepatic inflammation, and activates autophagy associated with high-fat diet–induced fatty liver hemorrhagic syndrome in aged laying hens

Abstract

The aim of this study was to investigate the effects of osteocalcin ( OCN ) on fatty liver hemorrhagic syndrome ( FLHS ) in aged laying hens. Thirty 68-week-old White Plymouth laying hens were randomly assigned into conventional single-bird cages, and the cages were randomly allocated into one of 3 treatments (n = 10): normal diet (ND + vehicle, ND + V ), high-fat diet (HFD + vehicle, HFD + V ), and HFD + OCN (3 μg/bird, 1 time/2 d, i.m.) for 40 d. At day 30, oral glucose tolerance tests ( OGTT ) and insulin tolerance tests ( ITT ) were performed. At the end of experiment, the hens were euthanized followed by blood collection. The plasma aspartate transaminase ( AST ), alkaline phosphatase ( ALP ), total cholesterol ( TC ), triglyceride ( TG ), low-density lipoprotein cholesterol ( LDL-C ), and high-density lipoprotein cholesterol ( HDL-C ) were measured using an automatic biochemistry analyzer. Pathological changes in the liver were examined under both light and transmission electron microscopes. The plasma inflammatory factors including interleukin-1 ( IL-1 ), IL-6, and tumor necrosis factor-alpha ( TNF-α ) were analyzed by ELISA, and the gene expressions of these inflammatory factors in the liver were analyzed by real-time PCR. The level of oxidative stress was evaluated using malondialdehyde ( MDA ) and glutathione peroxidase ( GSH-Px ) assay kits, respectively. The results showed that HFD + V hens had more severe liver hemorrhage and fibrosis than ND + V hens ( P < 0.05). The ultramicrostructural examination showed that hepatocytes of HFD + V hens exhibited necrotic pyknosis showing great intracellular electron, mitochondrial swelling, shrunk nucleus, and absence of autolysosomes. Osteocalcin mitigated HFD + V–induced pathological changes in aged laying hens. High-fat diet + OCN hens had higher insulin sensitivity; lower liver concentrations of MDA ( P = 0.12) but higher GSH-Px ( P < 0.05); and lower blood TNF-α concentrations ( P < 0.05) and mRNA expressions ( P < 0.05) than HFD + V hens. These results suggest OCN functions in preventing the FLHS process in old laying hens through inhibiting excessive energy diet-induced metabolic disorder, oxidative stress, and related pathological damage.

Effect of Flaxseed Supplementation on Milk and Plasma Fatty Acid Composition and Plasma Parameters of Holstein Dairy Cows

“…High-fat diets can cause fatty liver hemorrhagic syndrome in animals [ 67 ]. Plasma AST and ALP are used as indicators to reflect liver damage [ 68 ], and high levels lead to liver damage [ 69 ]. Previous studies reported that ALP showed a positive correlation with PUFA in milk [ 20 ].…”

Improvement of Lipotoxicity-Induced Islet β Cellular Insulin Secretion Disorder by Osteocalcin

“…Especially, the secretion of insulin was obviously increased. After intervention with exogenous OCN in mice fed with high fat and high glucose, the fat thickness of mice was decreased, but the insulin secretion and sensitivity were increased [22][23][24][25].…”

“…Meanwhile, OCN may regulate energy metabolism and have endocrine activity [16,20,21]. After intervention with exogenous OCN, the fat thickness of mice fed with high fat and high glucose was decreased, but the insulin secretion and sensitivity were increased [22][23][24][25]. Previous study showed that OCN treatment improved glucose homeostasis and lipid metabolism [26].…”

Dietary γ-Aminobutyric Acid Supplementation Inhibits High-Fat Diet-Induced Hepatic Steatosis via Modulating Gut Microbiota in Broilers

“…The pathological mechanisms of fatty liver in chickens are similar to nonalcoholic fatty liver disease (NAFLD), including insulin resistance, inflammation, and liver oxidative stress [ 23 ]. The multiple-hit pathogenesis theory considered that long-term hepatic fat accumulation can produce lipotoxicity, resulting in impairment of hepatocyte function and reduction of antioxidant capacity [ 24 ].…”