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- Carlsson, Björn, 1958, et al.
(författare)
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Obese (ob) gene defects are rare in human obesity
- 1997
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Ingår i: Obesity Research. - 1071-7323 .- 1550-8528. ; 5:1, s. 30-5
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Tidskriftsartikel (refereegranskat)abstract
- Our knowledge of the role of the recently cloned ob-protein (leptin) in the regulation of body fat stores is largely derived from experiments performed in mice. Different mouse models exhibit abnormalities in ob-gene expression, with extreme overexpression in mice which lack bioactive ob-protein, have nonfunctional ob-receptors or hypothalamic lesions, and undetectable expression in mice with suggested defects in regulatory elements. The aim of this study is to examine if defects, corresponding to those in mice, exist in human obesity. Adipose tissue was obtained from 94 adult obese subjects and from six children who had developed obesity after surgery in the hypothalamic region. Total RNA was isolated and ob-gene expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blot. The coding region of the ob-gene was sequenced in both directions in the 94 obese adults. No mutations were detected in the coding region of the ob-gene and ob-gene expression was detectable in all subjects and none of the subjects had an extreme overexpression. There was no systematic increase in ob-expression in obese children with hypothalamic disease compared to their healthy brothers and sisters. These results show that severe abnormalities involving the ob-gene, analogous to those described in mouse models, are rare in human obesity. We therefore conclude that the cloning and subsequent analysis of the ob-gene has not provided information that can, by itself, explain the genetic component in the development of human obesity.
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| 3. |
- Karlsson, C, et al.
(författare)
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Human adipose tissue expresses angiotensinogen and enzymes required for its conversion to angiotensin II.
- 1998
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 83:11, s. 3925-9
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin II regulates blood pressure and may affect adipogenesis and adipocyte metabolism. Angiotensin II is produced by cleavage of angiotensinogen by renin and angiotensin-converting enzyme in the circulation. In addition, angiotensin II may be produced in various tissues by enzymes of the renin-angiotensin system (RAS) or the nonrenin-angiotensin system (NRAS). We have analyzed the expression of angiotensinogen and enzymes required for its conversion to angiotensin II in human adipose tissue. Northern blot demonstrated angiotensinogen expression in adipose tissue from nine obese subjects. Western blot revealed a distinct band of expected size of the angiotensinogen protein (61 kDa) in isolated adipocytes. RT-PCR, followed by Southern blot, demonstrated renin expression in human adipose tissue. Angiotensin-converting enzyme messenger RNA was detected by RT-PCR, and the identity of the PCR products was verified by restriction enzyme cleavage. Transcripts for cathepsin D and cathepsin G, components of the NRAS, were detected by RT-PCR, verified by restriction enzyme cleavage. We conclude that human adipose tissue expresses angiotensinogen and enzymes of RAS and NRAS. This opens the possibility that angiotensinogen-derived peptides, produced in adipose tissue itself, may affect adipogenesis and play a role in the pathogenesis of obesity.
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