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Title: Molecular cloning and expression of the carbohydrate response element binding protein gene and related genes involved in hepatic lipogenesis during post-hatch development of broiler chickens

item Proszkowiec-Weglarz, Monika
item Richards, Mark
item Rosebrough, Robert
item McMurtry, John

Submitted to: BARC Poster Day
Publication Type: Abstract Only
Publication Acceptance Date: 3/26/2007
Publication Date: 4/25/2007
Citation: Proszkowiec-Weglarz, M., Humphrey, B., Richards, M.P., Rosebrough, R.W., McMurtry, J.P., Angel, R. 2007. Expression of the carbohydrate response element binding protein gene and related genes involved in hepatic lipogenesis during post-hatch development of broiler chickens [abstract]. Eighteenth Annual BARC Poster Day. p. 40, Abstract Number 33.

Interpretive Summary:

Technical Abstract: Carbohydrate response element binding protein (ChREBP) and sterol regulatory element binding protein-1c (SREBP-1c) are known to be key regulators of glucose metabolism and lipid synthesis in mammals. Responding to changes in the level of glucose (ChREBP) and insulin (SREBP-1c), these two transcription factors regulate the expression of lipogenic enzyme genes such as acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FAS), stearoyl-CoA desaturase 1 (SCD1), ATP citrate lyase (ACL), and malic enzyme (ME). ChREBP dimerizes with Max-like protein X (Mlx) and the heterodimeric complex binds to carbohydrate response element sites in target gene promoters. Expression of ChREBP and SREBP-1c is controlled, in part, by the nuclear liver X receptor (LXR) which is also regulated by glucose binding. Since the ChREBP gene has not been identified in birds, the objectives of this work were to clone and sequence it and to determine the expression of ChREBP and related genes in broilers during post-hatch (PH) development. To determine mRNA expression by RT-PCR, total RNA was isolated from 10 different tissues from 3-wk-old birds and from the livers of birds at 0, 1, 2, 3, 4, 6 and 8 d PH that were fed or fasted for the initial 48 hr PH. ChREBP, Mlx, SREBP-1c and LXR gene homologues were expressed in all tissues examined at 3 wk PH. ChREBP demonstrated significant tissue-specific expression with the highest mRNA levels found in liver and duodenum and the lowest in heart and skeletal muscle. SREBP-1c mRNA levels were highest in liver, brain, duodenum and skeletal muscle, and lowest in pancreas. Mlx was expressed in all tissues with the highest mRNA levels found in kidney. LXR mRNA levels were lower in abdominal fat, pancreas and hypothalamus compared to other tissues. Fasting for 48 hr PH did not change the level of ChREBP or Mlx mRNAs in liver; whereas, SREBP-1c mRNA level was lower at 48 hr in fasted as compared to fed chicks. Hepatic ACC1, FAS, SCD1, ACL and ME mRNA levels increased in response to feeding; however, fasting for 48 hr PH delayed this increase. Plasma levels of insulin increased and glucagon declined during the first 8 d PH, while fasting for 48 hr PH had no significant effect on the circulating levels of either hormone. We conclude that ChREBP, Mlx, SREBP-1c and LXR genes are actively expressed in chicken tissues throughout PH development. Together with LXR, ChREBP and Mlx could represent molecular components of a glucose-sensing mechanism that regulates lipid synthesis commensurate with energy (glucose) status. However, a definitive role for each of these transcription factors in glucose-dependent regulation of lipogenesis remains to be demonstrated in birds. Supported by USDA ARS CRIS Project No. 1265-31000-088-00D.