CIDEA
Cell death activator CIDE-A (Cell death-inducing DFFA-like effector A)
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Growth hormone (GH) administration reduces abdominal, but not lower body, fat mass. To gain insight into the underlying mechanisms, this study examined the expression of the GH receptor (GHR) and some of its targets in abdominal and gluteal adipose tissue. GHR and GH targets in the lipolytic pathway were assessed (quantitative PCR/Western blotting) in adipose aspirates from premenopausal women [n = 15, age 26.9 ± 6.1 years, body mass index (BMI) 28.0 ± 6.8 kg/m(2) ] and men (n = 28, age 29.2 ± 7.0 years, BMI 26.9 ± 3.7 kg/m(2) ). GHR mRNA expression was lower in the gluteal depot when compared with the abdominal depot (P = 0.01). Abdominal GHR correlated negatively with age and BMI, whereas gluteal GHR was associated with lower waist-to-hip ratio (WHR), that is, pear shape. In both sites, GHR mRNA correlated strongly with genes important for the regulation of lipolysis: adipose tissue triglyceride lipase (ATGL), hormone-sensitive lipase, perilipin, and CIDEA (all P < 0.001), independently of BMI, WHR, age, and sex. GHR protein was lower in the gluteal fat when compared with the abdominal fat (P = 0.03) and correlated with ATGL protein in the gluteal depot (P < 0.001). GHR levels correlate with levels of lipases and lipid droplet-associated proteins crucial for lipolysis. Thus, higher GHR expression in the abdominal depot when compared with the gluteal depot may underlie the in vivo effect of GH to specifically reduce abdominal adipose tissue mass.
MeSH Terms
- Adipose Tissue
- Adiposity
- Adult
- Aging
- Body Mass Index
- Buttocks
- Carrier Proteins
- Female
- Gene Expression
- Human Growth Hormone
- Humans
- Lipase
- Lipolysis
- Male
- Obesity
- Premenopause
- RNA, Messenger
- Receptors, Somatotropin
- Subcutaneous Fat, Abdominal
- Waist-Hip Ratio
Hypothermia induced by cold exposure at birth is prevented in sheep by the rapid onset of non-shivering thermogenesis in brown adipose tissue (BAT). Changes in adipose tissue composition in early life are therefore essential for survival but also influence adiposity in later life and were thus examined in detail during early development. Changes in adipose composition were investigated by immunohistochemistry and qRT-PCR between the period from the first appearance of adipose in the mid gestation foetus, through birth and up to 1 month of age. We identified four distinct phases of development, each associated with pronounced changes in tissue histology and in distribution of the BAT specific uncoupling protein (UCP)1. At mid gestation, perirenal adipose tissue exhibited a dense proliferative, structure marked by high expression of KI-67 but with no UCP1 or visible lipid droplets. By late gestation large quantities of UCP1 were present, lipid storage was evident and expression of BAT-related genes were abundant (e.g. prolactin and β3 receptors). Subsequently, within 12 h of birth, the depot was largely depleted of lipid and expression of genes such as UCP1, PGC1α, CIDEA peaked. By 30 days UCP1 was undetectable and the depot contained large lipid droplets; however, genes characteristic of BAT (e.g. PRDM16 and BMP7) and most characteristic of white adipose tissue (e.g. leptin and RIP140) were still abundant. Adipose tissue undergoes profound compositional changes in early life, of which an increased understanding could offer potential interventions to retain BAT in later life.
MeSH Terms
- Adipose Tissue, Brown
- Adiposity
- Aging
- Animals
- Lipid Metabolism
- Sheep
Keywords
- brown
- uncoupling protein
- white
Cell death-inducing DNA fragmentation factor-alpha-like effector A (CIDEA) could be a potential target for the treatment of obesity via the modulation of metabolic rate, based on the findings that CIDEA inhibits the brown adipose tissue uncoupling process in rodents. Our objects were to investigate the putative link between CIDEA and basal metabolic rate in humans and to elucidate further the role of CIDEA in human obesity. We have explored CIDEA gene expression in adipose tissue in two different human studies: a cross-sectional and population-based study assessing body composition and metabolic rate (Mölndal Metabolic study, n = 92); and a longitudinal intervention study of obese subjects treated with a very low calorie diet (VLCD) (VLCD study, n = 24). The CIDEA gene was predominantly expressed in adipocytes as compared with other human tissues. CIDEA gene expression in adipose tissue was inversely associated with basal metabolic rate independently of body composition, age, and gender (P = 0.014). The VLCD induced an increase in adipose tissue CIDEA expression (P < 0.0001) with a subsequent decrease in response to refeeding (P < 0.0001). Reduced CIDEA gene expression was associated with a high body fat content (P < 0.0001) and high insulin levels (P < 0.01). No dysregulation of CIDEA expression was observed in individuals with the metabolic syndrome when compared with body mass index-matched controls. In a separate sample of VLCD-treated subjects (n = 10), uncoupling protein 1 expression was reduced during diet (P = 0.0026) and inversely associated with CIDEA expression (P = 0.0014). The findings are consistent with the concept that CIDEA plays a role in adipose tissue energy expenditure.
MeSH Terms
- Adipocytes
- Adipose Tissue
- Adult
- Aging
- Anthropometry
- Apoptosis Regulatory Proteins
- Body Composition
- Caloric Restriction
- Cross-Sectional Studies
- Female
- Gene Expression
- Humans
- Ion Channels
- Longitudinal Studies
- Male
- Metabolic Syndrome
- Metabolism
- Middle Aged
- Mitochondrial Proteins
- Obesity
- Oligonucleotide Array Sequence Analysis
- Population
- RNA
- Reverse Transcriptase Polymerase Chain Reaction
- Sex Characteristics
- Uncoupling Protein 1