title: Increased expression of transthyretin in leptin-deficient ob/ob mice is not causative for their major phenotypic abnormalities.
abstract: The hormone leptin is a critical regulator of adipogenesis and energy metabolism. Similarly, leptin-deficient ob/ob 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 ob/ob mice, we observed the increased expression of the gene for transthyretin (Ttr) in the latter, as confirmed by quantitative real-time-polymerase chain reaction. Because Ttr encodes a carrier protein for retinol transport, and because we further found increased retinol levels in the serum of ob/ob mice, we investigated whether the additional absence of Ttr would influence the ob/ob phenotype. It was found that Ttr-deficient ob/ob mice were indistinguishable from ob/ob 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 Ttr-deficient mice, we found that the sole deletion of Ttr 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 Ttr-deficient ob/ob 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 Ttr in ob/ob mice does not cause (but rather attenuates) their phenotypic abnormalities.
authors: Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: C
authors: C
authors: Rendenbach
authors: S
authors: S
authors: Ganswindt
authors: S
authors: S
authors: Seitz
authors: F
authors: F
authors: Barvencik
authors: A K
authors: AK
authors: Huebner
authors: A
authors: A
authors: Baranowsky
authors: T
authors: T
authors: Streichert
authors: A
authors: A
authors: Niemeier
authors: J
authors: J
authors: Heeren
authors: M
authors: M
authors: Amling
authors: A
authors: A
authors: Bartelt
authors: T
authors: T
authors: Schinke
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D001842:Bone and Bones / Q000378:metabolism; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism; D005260:Female; D007031:Hypothalamus / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D020738:Leptin / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008820:Mice, Obese; D009154:Mutation; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011228:Prealbumin / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D020738:Leptin; D011228:Prealbumin; D012333:RNA, Messenger