Impaired hepatic mitochondrial function during early lactation in dairy cows: Association with protein lysine acetylation

Abstract

Early lactation is an energy-demanding period for dairy cows which may lead to negative energy balance, threatening animal health and consequently productivity. Herein we studied hepatic mitochondrial function in Holstein-Friesian multiparous dairy cows during lactation, under two different feeding strategies. During the first 180 days postpartum the cows were fed a total mixed ration (70% forage: 30% concentrate) ad libitum (non-grazing group, G0) or grazed Festuca arundinacea or Mendicago sativa plus supplementation (grazing group, G1). From 180 to 250 days postpartum, all cows grazed Festuca arundinacea and were supplemented with total mixed ration. Mitochondrial function was assessed measuring oxygen consumption rate in liver biopsies and revealed that maximum respiratory rate decreased significantly in grazing cows during early lactation, yet was unchanged in non-grazing cows during the lactation curve. While no differences could be found in mitochondrial content or oxidative stress markers, a significant increase in protein lysine acetylation was found in grazing cows during early lactation but not in cows from the non-grazing group. Mitochondrial acetylation positively correlated with liver triglycerides and β-hydroxybutyrate plasma levels, well-known markers of negative energy balance, while a negative correlation was found with the maximum respiratory rate and sirtuin 3 levels. To our knowledge this is the first report of mitochondrial function in liver biopsies of dairy cows during lactation. On the whole our results indicate that mitochondrial function is impaired during early lactation in grazing cows and that acetylation may account for changes in mitochondrial function in this period. Additionally, our results suggest that feeding total mixed ration during early lactation may be an efficient protective strategy.

Protein acetylation in mitochondria plays critical functions in the pathogenesis of fatty liver disease

“…Actually, mitochondria are crucial for cellular energy metabolism processes, including the production of more than 90% of cellular ATP (respiratory chain), tricarboxylic acid cycle, β-oxidation, apoptosis, cell-cycle progression, proliferation and aging, and their dysfunction has been implicated in a wide range of metabolic diseases [36,[42][43][44]. Recently, a significant increase in protein lysine acetylation was found in pasture-fed Holstein-Friesian dairy cows during their early lactation period, accounting for impaired hepatic mitochrondrial function [45]. Low expression of sirtuin 1 (SIRT1), a NAD-dependent histone deacetylase, was indicated to promote hepatic fatty acid synthesis and inhibit fatty acid β-oxidation in dairy cows with mild fatty liver disease [46].…”

“…Histone acetyltransferses (HATs) and histone deacetylase (HDACs), as a senor of environmental nutrient and/or energy, balance the acetylation level of target proteins. Mammalian sirtuins (SIRTs) is an important type of NAD-dependent histone deacetylase, such as SIRT1 and SIRT3, were involved in oxidative stress and lipid metabolism regulation [47], and had been proposed as a reliable biomarker and/or therapeutic target for fatty liver disease [45][46][47][48][49]. It suggests that acetylation of mitochondrial protein was an emerging and fundamental mechanism regulating the development of fatty liver disease in dairy cows, through modifying the activities of mitochondrial proteins and overall mitochondrial function [47][48][49].…”

Identification of Crucial Genetic Factors, Such as PPARγ, that Regulate the Pathogenesis of Fatty Liver Disease in Dairy Cows Is Imperative for the Sustainable Development of Dairy Industry

“…The fatty liver disease that occurs in dairy cows is a good animal model to reveal the pathology and pathogenesis of NAFLD. More recent study suggests that impaired hepatic mitochondrial function (such as protein lysine acetylation) is closely associated with fatty liver disease during early lactation in dairy cows [43,84]. Determining the crucial genetic factors, such as PPARγ, will also provide essential clues in breeding improvement of fatty liver disease-resistant dairy cattle, eventually contributing to sustainable development of dairy industry.…”

“…Oxidative stress may be exacerbated further by ultrastructural mitochondrial lesions, which impair respiratory chain function. Insulin inhibits β-oxidation in the mitochondria through modifying the protein acetylation [83][84][85], resulting in the accumulation of lipids in hepatocytes.…”

Effect of Chromium Methionine Supplementation on the Lactation Performance, Hepatic Respiratory Rate and Antioxidative Capacity of Early-Lactating Dairy Cows

“…The increased pyruvate, LDH and NADH activities in the plasma of dairy cows with increasing Cr-Met supplementation indicated that hepatic cellular respiration was improved by Cr-Met supplementation. The increased hepatic respiratory rate would lead to a greater level of hepatic gluconeogenesis in dairy cows [31]. Moreover, greater hepatic gluconeogenesis is associated with decreased insulin concentrations in the plasma [32].…”