Whole-transcriptome analysis of mouse adipose tissue in response to short-term caloric restriction

Abstract

Caloric restriction (CR) has been shown to extend the lifespan of many species by improving cellular function and organismal health. Additionally, fat reduction by CR may play an important role in lengthening lifespan and preventing severe age-related diseases. Interestingly, CR induced the greatest transcriptome change in the epididymal fat of mice in our study. In this transcriptome analysis, we identified and categorized 446 genes that correlated with CR level. We observed down-regulation of several signaling pathways, including insulin/insulin-like growth factor 1 (insulin/IGF-1), epidermal growth factor (EGF), transforming growth factor beta (TGF-β), and canonical wingless-type mouse mammary tumor virus integration site (Wnt). Many genes related to structural features, including extracellular matrix structure, cell adhesion, and the cytoskeleton, were down-regulated, with a strong correlation to the degree of CR. Furthermore, genes related to the cell cycle and adipogenesis were down-regulated. These biological processes are well-identified targets of insulin/IGF-1, EGF, TGF-β, and Wnt signaling. In contrast, genes involved in specific metabolic processes, including the tricarboxylic acid cycle and the electron transport chain were up-regulated. We performed in silico analysis of the promoter sequences of CR-responsive genes and identified two associated transcription factors, Paired-like homeodomain 2 (Pitx2) and Paired box gene 6 (Pax6). Our results suggest that strict regulation of signaling pathways is critical for creating the optimal energy homeostasis to extend lifespan.

Knockout of the X‐linkedFgf13in the hypothalamic paraventricular nucleus impairs sympathetic output to brown fat and causes obesity

“…That the b3 adrenoreceptor agonist stimulation revealed no intrinsic defect in BAT in Fgf13 +/2 mice was unexpected in the context of multiple studies that reported differential expression of Fgf13 in adipose in response to high-fat feeding or starvation (21)(22)(23)(24)(25). We therefore investigated specifically whether Fgf13 in adipose contributed to the observed metabolic phenotypes.…”

“…We and others have characterized Fgf13 effects on cardiac function (13,14,20,(39)(40)(41), neuronal migration during development (19), epileptogenesis (12), and ion channel trafficking and targeting in the axon initiation segment of cultured hippocampal neurons (42), yet gene ablation studies have not been employed to investigate roles for Fgf13 in metabolism, despite multiple studies reporting differential expression in adipose tissue in response to alterations in diet and in different obesogenic genetic backgrounds (21)(22)(23)(24)(25). To begin to investigate metabolic functions we generated a global Fgf13 knockout mouse model on a C57BL/6J background.…”

“…These observations suggest that the full complement of FGF13 functions is not fully defined. Moreover, multiple unbiased screens reported differential Fgf13 expression within adipose tissues in response to alterations in diet and in different obesogenic genetic backgrounds, as well as association of FGF13 with obesity in humans (21)(22)(23)(24)(25)(26), but the roles of Fgf13 in metabolism and obesity have not been investigated directly.…”

The effects of graded levels of calorie restriction: IX. Global metabolomic screen reveals modulation of carnitines, sphingolipids and bile acids in the liver of C57BL/6 mice

“…In contrast with earlier studies, which typically included a single treatment level, we used graded CR treatment groups (but see also Nogueira et al ., 2012; Kim et al ., 2016). This design enabled us to show not only that there was an increasing number of SDE metabolites with increasing CR, but also that many of these metabolites, including L‐carnitine, S1P and taurocholic acid, were increasingly upregulated with increasing CR.…”

Use of short-term high energy dietary for estimating transcriptional profiling of liver tissues in sheep

“…Nutrition plays a crucial role in regulating the growth and reproductive performance of farm animals. Energy homeostasis exerts a significant influence on animal health and body condition [1]. Positive energy balance results in increased leptin and insulin concentrations in the blood, which subsequently increased glucose uptake.…”