Increased Expression of Transthyretin in Leptin‐Deficient ob/ob Mice is not Causative for Their Major Phenotypic Abnormalities. (21st December 2012)

• Record Type: Journal Article
• Authors: Rendenbach, C.; Ganswindt, S.; Seitz, S.; Barvencik, F.; Huebner, A. K.; Baranowsky, A.; Streichert, T.; Niemeier, A.; Heeren, J.; Amling, M.; Bartelt, A.; Schinke, T.
• Is Part Of: Journal of neuroendocrinology. Volume 25:Number 1(2013:Jan.)
• Page Start: 14
• Page End: 22
• Publication Date: 2012-12-21
• Subjects: Neuroendocrinology -- Periodicals; 616.4
• DOI: 10.1111/j.1365-2826.2012.02366.x
• Languages: English
• ISSNs: 0953-8194

Abstract

<abstract abstract-type="main" xml:lang="en" id="jne2366-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The hormone leptin is a critical regulator of adipogenesis and energy metabolism. Similarly, leptin‐deficient <italic>ob/ob</italic> mice display various metabolic abnormalities, including not only obesity and insulin resistance, but also hypogonadism and high bone mass. By genome‐wide expression analysis using hypothalamus RNA from wild‐type and <italic>ob/ob</italic> mice, we observed the increased expression of the gene for <italic>transthyretin</italic> (<italic>Ttr</italic>) in the latter, as confirmed by quantitative real‐time‐polymerase chain reaction. Because <italic>Ttr</italic> encodes a carrier protein for retinol transport, and because we further found increased retinol levels in the serum of <italic>ob/ob</italic> mice, we investigated whether the additional absence of <italic>Ttr</italic> would influence the <italic>ob/ob</italic> phenotype. It was found that <italic>Ttr</italic>‐deficient <italic>ob/ob</italic> mice were indistinguishable from <italic>ob/ob</italic> littermates in terms of body weight, as well as serum glucose, insulin and cholesterol levels. Although all of these parameters were identical to wild‐type controls in <italic>Ttr</italic>‐deficient mice, we found that the sole deletion of <italic>Ttr</italic> caused a significant increase of trabecular bone mass, bone marrow adiposity and mean adipocyte area in white adipose tissue. Interestingly, all these latter parameters were highest in <italic>Ttr</italic>‐deficient <italic>ob/ob</italic> mice, and only in these mice did we observe a full penetrance of liver steatosis at 24 weeks of age. Taken together, our data demonstrate that the increased expression of <italic>Ttr</italic> in <italic>ob/ob</italic> mice does not cause (but rather attenuates) their phenotypic abnormalities.</p> </abstract>