Department of Clinical & Experimental Medicine - Federico II University Medical School, Via Pansini 5, 80131, Naples, Italy.
Cell Biology International (Impact Factor: 1.64). 06/2013; DOI: 10.1002/cbin.10145
Source: PubMed

ABSTRACT Fat distribution is associated with metabolic risk; differences in cellular characteristics and metabolic functions of these depots have been described, but the molecular mechanisms involved are not understood. The pathogenesis and pathophysiology of metabolic disease can well be understood by studying the molecular mechanisms that control the development and function of adipose tissue (adipogenesis). Homeobox genes are transcription factors that act during normal development and contain the homeobox, a 183bp DNA sequence coding for a 61 amino acid domain defined as homeodomain (HD). Class 1 homeobox genes (Hox genes) have a critical role in controlling positional information and tissue patterning during development. The expression of the whole HOX gene network in different deposits of normal adult human white adipose tissue (intraperitoneal, extra-peritoneal, and dermis) indicate a marked expression in adipose tissue. Furthermore this expression seems to vary in different bodily deposits of white adipose tissue and between white and brown adipose tissue. The purpose of this mini-review is to discuss the role of HOX genes in metabolic diseases.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Insulin gene expression is restricted to islet cells of the mammalian pancreas through specific control mechanisms mediated in part by specific transcription factors1, 2. The protein encoded by the pancreatic and duodenal homeobox gene 1 (PDX-1) is central in regulating pancreatic development and islet cell function3. PDX-1 regulates insulin gene expression and is involved in islet cell-specific expression of various genes4, 5, 6, 7. Involvement of PDX-1 in islet-cell differentiation and function has been demonstrated mainly by 'loss-of-function' studies8, 9, 10, 11. We used a 'gain-of-function' approach to test whether PDX-1 could endow a non-islet tissue with pancreatic -cell characteristics in vivo. Recombinant-adenovirus-mediated gene transfer of PDX-1 to the livers of BALB/C and C57BL/6 mice activated expression of the endogenous, otherwise silent, genes for mouse insulin 1 and 2 and prohormone convertase 1/3 (PC 1/3). Expression of PDX-1 resulted in a substantial increase in hepatic immunoreactive insulin content and an increase of 300% in plasma immunoreactive insulin levels, compared with that in mice treated with control adenovirus. Hepatic immunoreactive insulin induced by PDX-1 was processed to mature mouse insulin 1 and 2 and was biologically active; it ameliorated hyperglycemia in diabetic mice treated with streptozotocin. These data indicate the capacity of PDX-1 to reprogram extrapancreatic tissue towards a -cell phenotype, may provide a valuable approach for generating 'self' surrogate cells, suitable for replacing impaired islet-cell function in diabetics.
    Nature Medicine 04/2000; 6(5):568-572. · 22.86 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Many chromosome regions in the human genome exist in four similar copies, suggesting that the entire genome was duplicated twice in early vertebrate evolution, a concept called the 2R hypothesis. Forty-two gene families on the four Hox-bearing chromosomes were recently analyzed by others, and 32 of these were reported to have evolutionary histories incompatible with duplications concomitant with the Hox clusters, thereby contradicting the 2R hypothesis. However, we show here that nine of the families have probably been translocated to the Hox-bearing chromosomes more recently, and that three of these belong to other chromosome quartets where they actually support the 2R hypothesis. We consider 13 families too complex to shed light on the chromosome duplication hypothesis. Among the remaining 20 families, 14 display phylogenies that support or are at least consistent with the Hox-cluster duplications. Only six families seem to have other phylogenies, but these trees are highly uncertain due to shortage of sequence information. We conclude that all relevant and analyzable families support or are consistent with block/chromosome duplications and that none clearly contradicts the 2R hypothesis.
    Genome Research 01/2003; 12(12):1910-20. · 14.40 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We previously used an integrative genetics approach to demonstrate that 5-lipoxygenase (5-LO) deficiency in mice (Alox5 (-/-)) protects against atherosclerosis despite increasing lipid levels and fat mass. In the present study, we sought to further examine the role of 5-LO in adiposity and pancreatic function. Alox5 (-/-) and wild-type (WT) mice were characterised with respect to adiposity and glucose/insulin metabolism using in vivo and in vitro approaches. The role of ALOX5 in pancreatic function in human islets was assessed through short interfering RNA (siRNA) knockdown experiments. Beginning at 12 weeks of age, Alox5 (-/-) mice had significantly increased fat mass, plasma leptin levels and fasting glucose levels, but lower fasting insulin levels (p<0.05). Although Alox5 (-/-) mice did not exhibit insulin resistance, they had impaired insulin secretion in response to a bolus glucose injection. Histological analyses revealed that Alox5 (-/-) mice had increased islet area, beta cell nuclear size, and numbers of beta cells/mm(2) islet (p<0.05), indicative of both hyperplasia and hypertrophy. Basal and stimulated insulin secretion in isolated Alox5 (-/-) islets were significantly lower than in WT islets (p<0.05) and accompanied by a three- to fivefold decrease in the expression of the genes encoding insulin and pancreatic duodenal homeobox 1 (Pdx1). Direct perturbation of ALOX5 in isolated human islets with siRNA decreased insulin and PDX1 gene expression by 50% and insulin secretion by threefold (p<0.05). These results provide strong evidence for pleiotropic metabolic effects of 5-LO on adiposity and pancreatic function and may have important implications for therapeutic strategies targeting this pathway for the treatment of cardiovascular disease.
    Diabetologia 06/2008; 51(6):978-88. · 6.49 Impact Factor


Available from
May 26, 2014

Similar Publications