Transcriptional regulation of metabolic genes in the liver is the key to maintaining systemic energy homeostasis during starvation. The membrane-bound transcription factor cAMP-responsive element-binding protein 3-like 3 (CREB3L3) has been reported to be activated during fasting and to regulate triglyceride metabolism. Here, we show that CREB3L3 confers a wide spectrum of metabolic responses to starvation in vivo. Adenoviral and transgenic overexpression of nuclear CREB3L3 induced systemic lipolysis, hepatic ketogenesis, and insulin sensitivity with increased energy expenditure, leading to marked reduction in body weight, plasma lipid levels, and glucose levels. CREB3L3 overexpression activated gene expression levels and plasma levels of antidiabetic hormones, including fibroblast growth factor 21 and IGF-binding protein 2. Amelioration of diabetes by hepatic activation of CREB3L3 was also observed in several types of diabetic obese mice. Nuclear CREB3L3 mutually activates the peroxisome proliferator-activated receptor (PPAR) α promoter in an autoloop fashion and is crucial for the ligand transactivation of PPARα by interacting with its transcriptional regulator, peroxisome proliferator-activated receptor gamma coactivator-1α. CREB3L3 directly and indirectly controls fibroblast growth factor 21 expression and its plasma level, which contributes at least partially to the catabolic effects of CREB3L3 on systemic energy homeostasis in the entire body. Therefore, CREB3L3 is a therapeutic target for obesity and diabetes.

No abstract

Using high-performance liquid chromatography, 11 sulfur-containing flavor precursors were determined quantitatively in seven Allium vegetables: garlic (Allium sativum), onion (A. cepa), Welsh onion (A. fistulosum), Chinese chive (A. tuberosum Rotter), rakkyo (A. chinense G. Don), 'asatsuki' (A. schoenoprasum), and leek (A. porrum). Keywords: alliin, Alliums, flavor precursor, glutamyl peptide, high-performance liquid chromatography, isoalliin, S-alk(en) yl-L-cysteine *To whom correspondence should be addressed. E-mail: yoshihisa_yamazaki@aomori-itc.or.jp The determinants were S-alk(en)yl-L-cysteine derivatives, methiin, alliin, isoalliin, cycloalliin, deoxyalliin, N-(γ-glutamyl)-S-methyl-L-cysteine, N-(γ-glutamyl)-S-(2-propenyl)-L-cysteine, N-(γ-glutamyl)-S-(E-1-propenyl)-L-cysteine (Glu-PEC), N-(γ-glutamyl)-S-(2-propenyl)-Lcysteine sulfoxide, N-(γ-glutamyl)-S-(E-1-propenyl)-L-cysteine sulfoxide (Glu-PECSO) and S-(2-carboxy IntroductionAllium vegetables, such as garlic (A. sativum L.) and onion (A. cepa L.), have been used as seasoning vegetables worldwide (Block, 1992(Block, , 2010. Allium vegetables contain large amounts of S-alk(en)yl-L-cysteine derivatives (SACs, Fig. 1) (Kubec et al., 2000). When these vegetables are cut or crushed, S-alk(en)yl-L-cysteine sulfoxides (SACSOs), i.e., methiin, alliin, isoalliin, are cleaved by alliinase (cysteine sulfoxide lyase: EC 4.4.1.4) to give the corresponding alk(en) yl sulfenic acids (Stoll and Seebeck, 1951). The sulfenic acids are transformed via continuous reactions to thiosulfinates (e.g., diallyl thiosulfinate (allicine)) and other organosulfur volatile compounds (e.g., diallyl disulfide) to produce characteristic flavors . These organosulfur volatile compounds have been reported as flavor compounds of food, in addition to bioactive compounds (Block, 1994), or causal compounds of processed food discoloration (Kubec et al., 2004;Imai et al., 2006).The degrees of the respective contributions of these organosulfur volatile compounds to flavor, bioactivity, and food discoloration depend on their alkyl moieties: they are dominated by the kinds and quantities of SACSO as substrates of alliinase in Allium vegetables. Allium vegetables also contain γ-glutamyl peptides of S-alk(en)yl-L-cysteine (Glu-SAC) corresponding to SACSOs that are storage compounds during dormancy (Tuboi et al., 1989;Lancaster and Shaw, 1991;Lawson et al., 1991;Ichikawa et al., 2006b). These SACSOs as well as Glu-SAC in Allium vegetables should be evaluated as Glu-SAC is metabolized to SACSO depending on the storage conditions.Comparing the contents of SACs in individual Allium ical Industries Ltd. (Osaka, Japan). Water purified using a Milli-Q instrument (Millipore Corp., MA, USA) was used for all sample preparations and mobile phases. Reference compounds, and N-(γ-glutamyl)-S-(2-propenyl)-L-cysteine sulfoxide (Glu-ALCSO) (98%) were isolated from garlic cloves. Isoalliin (99%), N-(γ-glutamyl)-S-(E-1-propenyl)-L-cysteine sulfoxide (Glu-PECSO) (96%), and S-2-carboxy propyl gluthathion (2CPGTH) (98%) ...

No abstract