title: Factor for adipocyte differentiation 158 gene disruption prevents the body weight gain and insulin resistance induced by a high-fat diet.
abstract: To clarify the molecular mechanism of adipocyte differentiation, we previously isolated a novel gene, factor for adipocyte differentiation (fad) 158, whose expression was induced during the earliest stages of adipogenesis, and its product was localized to the endoplasmic reticulum. We found that the knockdown of fad158 expression prevented the differentiation of 3T3-L1 cells into adipocytes. In addition, over-expression of fad158 promoted the differentiation of NIH-3T3 cells, which do not usually differentiate into adipocytes. Although these findings strongly suggest that fad158 has a crucial role in regulating adipocyte differentiation, the physiological role of the gene is still unclear. In this study, we generated mice in which fad158 expression was deleted. The fad158-deficient mice did not show remarkable changes in body weight or the weight of white adipose tissue on a chow diet, but had significantly lower body weights and fat mass than wild-type mice when fed a high-fat diet. Furthermore, although the disruption of fad158 did not influence insulin sensitivity on the chow diet, it improved insulin resistance induced by the high-fat diet. These results indicate that fad158 is a key factor in the development of obesity and insulin resistance caused by a high-fat diet.
authors.affiliation: Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hayashi
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Nozaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishizuka
authors.forename: Masahito
authors.initials: M
authors.lastname: Ikawa
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Osada
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Imagawa
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology*; D050156:Adipogenesis / Q000235:genetics*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects*; D007333:Insulin Resistance / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D015430:Weight Gain / Q000235:genetics*
chemical_list: D004041:Dietary Fats; C570293:FAD158 protein, mouse; D008565:Membrane Proteins