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Cyclic AMP-responsive element-binding protein H (CREBH encoded by Creb3l3) is a transcription factor that regulates the expression of genes that control lipid and glucose metabolism as well as inflammation. CREBH is upregulated in the liver under conditions of overnutrition, and mice globally lacking the gene (CREBH -/- ) are highly susceptible to diet-induced obesity, insulin resistance, and hepatic steatosis. The net protective effects of CREBH have been attributed in large part to the activities of fibroblast growth factor (Fgf)-21 (Fgf21), a target gene that promotes weight loss, improves glucose homeostasis, and reduces hepatic lipid accumulation. To explore the possibility that activation of the CREBH-Fgf21 axis could ameliorate established effects of high-fat feeding, we generated an inducible transgenic hepatocyte-specific CREBH overexpression mouse model (Tg-rtTA). Acute overexpression of CREBH in livers of Tg-rtTA mice effectively reversed diet-induced obesity, insulin resistance, and hepatic steatosis. These changes were associated with increased activities of thermogenic brown and beige adipose tissues in Tg-rtTA mice, leading to reductions in fat mass, along with enhanced insulin sensitivity and glucose tolerance. Genetically silencing Fgf21 in Tg-rtTA mice abrogated the CREBH-mediated reductions in body weight loss, but only partially reversed the observed improvements in glucose metabolism. These findings reveal that the protective effects of CREBH activation may be leveraged to mitigate diet-induced obesity and associated metabolic abnormalities in both Fgf21-dependent and Fgf21-independent pathways., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Modern dairy cows meet the energy demand of early lactation by calling on hormonally driven mechanisms to increase the use of lipid reserves. In this context, we recently reported that fibroblast growth factor-21 (FGF21), a hormone required for efficient use of lipid reserves in rodents, is upregulated in periparturient dairy cows. Increased plasma FGF21 in early lactation coincides with elevated circulating concentrations of glucagon (GCG) and nonesterified fatty acids (NEFA). To assess the relative contribution of these factors in regulating FGF21, two experiments were performed in energy-sufficient, nonpregnant, nonlactating dairy cows. In the first study, cows were injected with saline or GCG every 8 h over a 72-h period. GCG increased hepatic FGF21 mRNA by an average of fivefold over matched controls but had no effect on plasma FGF21. In the second study, cows were infused and injected with saline, infused with Intralipid and injected with saline, or infused with Intralipid and injected with GCG. Infusions and injections were administered intravenously over 16 h and subcutaneously every 8 h, respectively. Intralipid infusion increased plasma NEFA from 92 to 550 µM within 3 h and increased plasma FGF21 from 1.3 to >11 ng/ml 6 h later; FGF21 mRNA increased by 34-fold in liver but remained invariant in adipose tissue. GCG injections during the Intralipid infusion had no additional effects on plasma NEFA, liver FGF21 mRNA, or plasma FGF21. These data implicate plasma NEFA as a key factor triggering hepatic production and increased circulating concentrations of FGF21 in early lactation., (Copyright © 2017 the American Physiological Society.)

This study was designed to establish if Curcumin (CM) alleviates Aflatoxin B₁ (AFB₁)-induced hepatotoxic effects and to determine whether alteration of the expression of cytochrome P450 (CYP450) isozymes is involved in the regulation of these effects in chick liver. One-day-old male broilers ( n = 120) were divided into four groups and used in a two by two factorial trial in which the main factors included supplementing AFB₁ (< 5 vs. 100 μg/kg) and CM (0 vs. 150 mg/kg) in a corn/soybean-based diet. Administration of AFB₁ induced liver injury, significantly decreasing albumin and total protein concentrations and increasing alanine aminotransferase and aspartate aminotransferase activities in serum, and induced hepatic histological lesions at week 2. AFB₁ also significantly decreased hepatic glutathione peroxidase, catalase, and glutathione levels, while increasing malondialdehyde, 8-hydroxydeoxyguanosine, and exo-AFB₁-8,9-epoxide (AFBO)-DNA concentrations. In addition, the mRNA and/or activity of enzymes responsible for the bioactivation of AFB₁ into AFBO-including CYP1A1, CYP1A2, CYP2A6, and CYP3A4-were significantly induced in liver microsomes after 2-week exposure to AFB₁. These alterations induced by AFB₁ were prevented by CM supplementation. Conclusively, dietary CM protected chicks from AFB₁-induced liver injury, potentially through the synergistic actions of increased antioxidant capacities and inhibition of the pivotal CYP450 isozyme-mediated activation of AFB₁ to toxic AFBO., Competing Interests: The authors declare no conflict of interest.

This study was conducted to determine the effects of aflatoxin B1 (AFB1) on the hepatic transcriptome in ducklings through RNA-sequencing (RNA-Seq). Twenty four, 1-day-old ducklings were divided into 4 treatment groups. Each group received an oral dose of AFB1 at 0, 10, 20, 40 μg/kg BW per day for 2 weeks. Administration of 20 and 40 μg/kg BW of AFB1 significantly decreased body weight, feed intake, serum total protein and albumin, while increasing serum aspartate aminotransferase and alanine aminotransferase activities, and hepatic histopathological lesions. Furthermore, RNA was extracted from the liver of ducklings administrated 0 and 40 μg/kg BW of AFB1. Two RNA-Seq libraries were created from pooled samples and produced over 149 M reads, totaling 14.9 Gb of sequence. Approximately 96,953 predicted transcripts were assembled, 749 of which had significant differential expressions (≥ 2-fold) between the control and AFB1 treatment. GO and KEGG pathway analysis results showed that many genes involved in phase I metabolism, phase II detoxification, oxidation-reduction process, carcinogenesis, apoptosis and cell cycle, and fatty acid metabolism were affected by AFB1 exposure. Conclusion, this study determined the hepatic transcriptome responded to AFB1 exposure, and provide candidate genes can be targeted to prevent and/or reduce aflatoxicosis in ducklings., (Copyright © 2016 Elsevier Ltd. All rights reserved.)