EpiHeat - Heat stress-induced epigenetic regulation of hepatic metabolism and immunity in Holstein dairy cows

• Applicant: Dr. Franziska Koch
• Subject Area: Animal Breeding, Animal Nutrition, Animal Husbandry
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 537788574

The consequences of climate change become more expressed worldwide in the frequent occurrence of extreme weather phenomena and heat waves in summer months. Dairy cows are exposed to direct environmental influences due to open and semi-open farming systems. The imbalance between endogenous heat production and simultaneous heat dissipation leads to heat stress in dairy cows. Heat-stressed cows reduce feed intake and milk yield while increasing of respiratory frequency, heart rate, and activation of the immune response, jeopardizing animal health and welfare. The liver has a dual role in regulating the adaptive mechanism to cope with heat stress as an important switch between metabolic and immune response. On cellular level, rapid adjustments are required to orchestrate the hepatic immune and metabolic responses during heat stress. Epigenetic modifications as overarching regulatory mechanism are postulated to play an important role in coordinating the switch between metabolic to immunomodulatory adaptive mechanisms. Lysine acetylation of proteins might regulate the protein activity, protein stability and protein-protein interaction depending on nutrient availability during heat stress. The aim of the present DFG proposal is to investigate the effect of chronic heat stress on the epigenetic modifications of the liver on immune and metabolic adaptation depending on the metabolic status of lactating Holstein cows. A total of 30 Holstein cows were divided into three groups: heat stress (HS; 28°C, temperature-humidity index (THI) 76, ad libitum), control group (16°C, THI 60, ad libitum), or pair feeding (PF; 16°C, THI 60, with restrictive feeding). The PF group was necessary to account for the dual effect of heat stress with reduced feed intake and to ensure isoenergetic ratios between HS and PF animals. First, the effects of thermal heat on epigenetic modifications in the lysine acetylation pattern of the hepatic proteome will be investigated in relation to metabolism and immune response, and histone modifications of the liver will be analyzed in detail. In addition, morphological alterations and cellular damage in the liver of heat-stressed dairy cows will be characterized. Second, the hepatic immune response will be studied by focusing on Kupffer cell activation, pro-inflammatory cytokines and acute-phase protein production. New insights into the epigenetic regulation of hepatic function will contribute to the understanding of the underlying molecular mechanisms. From these new results, other feeding strategies may be identified to influence epigenetic changes during the hot summer and provide an alternative to standard practices.

• DFG Programme: Research Grants