Atf3 induction is a therapeutic target for obesity and metabolic diseases

Journal Article · Mon Oct 15 04:00:00 EDT 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.09.048· OSTI ID:23107866

Kim, Suji; Song, No-Joon ^[1]; Bahn, Gahee ^[2]; Chang, Seo-Hyuk; Yun, Ui Jeong ^[1]; Ku, Jin-Mo ^[3]; Jo, Dong-Gyu ^[2]

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1. Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon, 16419, South (Korea, Republic of)
2. School of Pharmacy, Sungkyunkwan University, Suwon, 16419, South (Korea, Republic of)
3. Biomaterials Research and Development Team, Bio-Center, Gyeonggido Business Science Accelerator, Suwon, 16229, South (Korea, Republic of)

Highlights: • Atf3 knockout mice increases body weight and impaired glucose tolerance in high fat diet fed mice. • Atf3 knockout mice increases body weight in chow diet fed aged mice. • Sulfuretin, a phytochemical Atf3 iducer, requires Atf3 expression to prevent obesity. Activating transcription factor 3 (Atf3) has been previously demonstrated to impact obesity and metabolism. However, a metabolic role of Atf3 in mice remains debatable. We investigated the role of Atf3 in mice and further investigated Atf3 expression as a therapeutic target for obesity and metabolic diseases. Atf3 knockout (KO) mice fed with a high fat diet (HFD) aggravated weight gain and impaired glucose metabolism compared to littermate control wild type (WT) mice. Atf3 KO aged mice fed with a chow diet (CD) for longer than 10 months also displayed increased body weight and fat mass compared to WT aged mice. We also assessed requirements of Atf3 in a phytochemical mediated anti-obese effect. Effect of sulfuretin, a previously known phytochemical Atf3 inducer, in counteracting weight gain and improving glucose tolerance was almost completely abolished in the absence of Atf3, indicating that Atf3 induction can be a molecular target for preventing obesity and metabolic diseases. We further identified other Atf3 small molecule inducers that exhibit inhibitory effects on lipid accumulation in adipocytes. These data highlight the role of Atf3 in obesity and further suggest the use of chemical Atf3 inducers for prevention of obesity and metabolic diseases.

• OSTI ID: 23107866
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 504; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
DIET
GLUCOSE
METABOLIC DISEASES
MICE