Protective effects of dietary dimethyl itaconate supplementation on oxidative stress, inflammation, and apoptosis in broilers under chronic heat stress.

This study was conducted to evaluate the effects of dietary dimethyl itaconate (DI) supplementation on oxidative stress, inflammation, and apoptosis in broilers under chronic heat stress (HS). Twenty-one-day-old male Ross 308 broilers (n = 120) were randomly allocated to 5 groups: a control group, HS group, HS + 50 mg/kg DI group, HS + 150 mg/kg DI group, and HS + 200 mg/kg DI group. The birds in the control group received the basal diets and were maintained at 21 ± 1 °C for 24 h daily. The birds in the HS group and HS + DI groups were raised at 32 ± 1 °C for 8 h daily and received basal diets containing DI at the indicated dose (0, 50, 150, or 200 mg/kg). The results showed that the contents of alanine aminotransferase, aspartate aminotransferase, and malondialdehyde (MDA) in serum were markedly elevated by exposure to chronic HS (P < 0.01), and this elevation was alleviated by 150 and 200 mg/kg DI supplementation (P < 0.05). Chronic HS-induced declines (P < 0.05) in total antioxidant capacity (T-AOC) and activities of peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) in serum were markedly attenuated after 200 mg/kg DI treatment in broilers (P < 0.05). Moreover, broilers subjected to chronic HS exhibited higher contents of MDA, protein carbonyl, and hydrogen peroxide (P < 0.01), but lower T-AOC and activities of antioxidant enzymes (P < 0.05), as well as reduced inhibition of superoxide and hydroxyl free radicals (P < 0.01) in the liver compared to the control group; these changes were effectively mitigated by treatment with 200 mg/kg DI in broilers (P < 0.05). In addition, 50-200 mg/kg DI effectively ameliorated chronic HS-stimulated upregulation of the mRNA levels of pro-inflammatory mediators in the livers of broilers (P < 0.01). Dietary supplementation with 150 and 200 mg/kg DI significantly alleviated chronic HS challenge-induced upregulation of the mRNA levels of Bcl-2-associated X, caspase 3, and caspase 9 (P < 0.01), but downregulation of Bcl-2 mRNA levels (P < 0.01) in broilers (P < 0.05). Importantly, chronic HS-induced downregulation of the mRNA or protein levels of nuclear factor (erythroid-derived 2)-like 2 (NRF-2), NADPH quinone acceptor oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), SOD2, or glutathione-S-transferases (GST) (P < 0.01) was markedly improved by 150 and 200 mg/kg DI (P < 0.05). The above results indicated that DI can ameliorate oxidative stress, inflammation, and apoptosis in broilers under chronic HS.

Global warming has become increasingly severe in recent years, threatening all life forms on Earth. Poultry are particularly susceptible to heat stress (HS) due to their unique physiological features, such as the absence of sweat glands and a high metabolic rate, and HS thus leads to liver injury and high mortality in broilers. Numerous studies have shown that dimethyl itaconate (DI) exerts beneficial effects in the regulation of inflammation, oxidative stress, and nutrient metabolism. However, it remains unclear whether DI can be used as a dietary supplement to prevent oxidative stress, inflammation, and apoptosis in broilers exposed to chronic HS. Here, we found that DI markedly relieved chronic HS-induced liver injury and enhancement of active molecule contents in the livers of broilers. Simultaneously, DI significantly ameliorated chronic HS by enhancing the antioxidative capacity and reducing the expression of pro-inflammatory cytokines and pro-apoptotic factors in broiler liver, which may be achieved through activation of the nuclear factor (erythroid-derived 2)-like 2 signaling pathway. These results may provide sufficient data to support DI as a dietary supplement for controlling diseases associated with chronic HS in broilers.

Dietary supplementation of dimethyl itaconate protects against chronic heat stress-induced growth performance impairment and lipid metabolism disorder in broiler chickens.

This study aimed to investigate the protective effects of dietary supplementation of dimethyl itaconate (DI) on chronic heat stress (HS)-induced impairment of the growth performance and lipid metabolism in broiler chickens. 21 days old male Ross 308 broiler chickens (a total of 120, about 700 g body weight) were randomly divided into five treatment groups, including control group, HS group, HS + 50 mg/kg DI group, HS + 150 mg/kg DI group, and HS + 200 mg/kg DI group, and each group contains eight cages of twenty-four broilers. The broiler chickens in the control group were raised in the room (21 ± 1 °C) and fed with a finisher diet for 21 days. The broiler chickens of the HS group and the HS + DI groups were raised in the room (32 ± 1 °C for 8 h/day) and fed with a finisher diet containing DI at 0, 50, 150, and 200 mg/kg diet for 21 days. The results showed that HS-induced decreases in the final body weight (P < 0.01), average daily gain (P < 0.01), and average daily feed intake (P < 0.01) were alleviated by dietary supplementation of DI (P < 0.05). In addition, dietary supplementation of DI attenuated the increases in the liver index (P < 0.01) and abdominal fat rate (P < 0.01) caused by HS in broilers (P < 0.05). Treatment with DI ameliorated HS-induced lipid accumulation in the liver and serum of broiler chickens (P < 0.05). The upregulation of mRNA levels of fat synthesis factors (P < 0.01) and downregulation of mRNA levels of lipolysis-related factors (P < 0.01) caused by HS were markedly blunted after treatment with DI in the liver of broilers (P < 0.05). Broilers exposed to HS exhibited lower phosphorylated protein levels of AMP-activated protein kinase α and acetyl-CoA carboxylase α compared to the control group (P < 0.01), which were improved by treatment with DI (P < 0.01). Collectively, these results demonstrated that dietary supplementation of DI protects against chronic HS-induced growth performance impairment and lipid metabolism disorder in broiler chickens. These results not only provide a theoretical basis for DI to alleviate metabolic disorders but also provide a reference value for DI as a feed additive to improve heat stress in poultry caused by high temperature.

Heat stress (HS) caused by high temperatures can lead to metabolic disorders and decreased growth performance in broilers, which has become a global concern in broiler production. Dimethyl itaconate (DI), as a cell-permeable itaconate derivative, has many benefits in alleviating inflammatory response and antioxidant. However, the beneficial effect of DI on broilers exposed to HS are still unclear. Here, we found that DI treatment improved the decline of growth performance and hormone secretion disorder caused by HS in broiler chickens. Moreover, the treatment with DI alleviated the excessive accumulation of lipids caused by HS through reducing mRNA levels related to liposynthesis and enhancing mRNA levels associated with lipolysis in broiler chickens, which may be achieved by activation of the AMP-activated protein kinase (AMPK) signaling pathway. These data not only provide the potential mechanism for DI to alleviate metabolic disorders but also provide a sufficient theoretical basis for DI as an additive to alleviate HS in broiler chickens.