Ectopic recombination in the central and peripheral nervous system by aP2/FABP4‐Cre mice: Implications for metabolism research

Abstract

Edited by Laszlo Nagy Keywords:Adipose tissue Conditional knockout mice Fatty acid binding protein 4 Sympathetic nervous system Peroxisomes Central nervous system Adipocyte a b s t r a c t aP2-Cre mice have amply been used to generate conditional adipose selective inactivation of important signaling molecules. We show that the efficiency of Cre mediated recombination in adipocytes and adipose selectivity is not always guaranteed. In particular, Cre activity was found in ganglia of the peripheral nervous system (PNS), in adrenal medulla and in neurons throughout the central nervous system (CNS). Because these tissues have an important impact on adipose tissue, care should be taken when using aP2-Cre mice to define the role of the targeted genes in adipose tissue function.

Altered miRNA processing disrupts brown/white adipocyte determination and associates with lipodystrophy

“…Creation of fat-specific dicer-KO mice also illustrates some of the important caveats of tissue-selective recombination in fat, as previously reported by us and others (35,57). Thus, in our first attempt to determine the role of dicer in adipose tissue, we created KO mice using aP2-Cre, and, as observed by Mudhasani et al (34), these aP2-Cre dicer fl/fl mice die shortly after birth and are much smaller and more fragile than their littermate controls.…”

Tuberous Sclerosis Complex 1–Mechanistic Target of Rapamycin Complex 1 Signaling Determines Brown-to-White Adipocyte Phenotypic Switch

“…Our studies further support this concept. However, it is worth of noting that our study cannot exclude the contribution of mTOR signaling in other metabolically critical organs because FABP4 is not exclusively expressed in BAT and WAT (26,35,36). While our in vitro studies suggest that mTOR signaling may determines the interconversion between brown and white adipocytes, a portion of the whitening of brown fat in Fabp4-Tsc1 2/2 transgenic mice could result from increased mTORC1 function in tissue other than adipose tissues such as brain, liver, and skeletal muscles.…”

Dietary obesity-associated Hif1α activation in adipocytes restricts fatty acid oxidation and energy expenditure via suppression of the Sirt2-NAD+ system

“…Littermates lacking the aP2-Cre-ERT2 transgene are termed Hif1a iC. This model permits the specific interrogation of Hif1a function in adult adipocytes and circumvents the problem of nonadipocyte Cre activation during embryogenesis and in early postnatal development that has been shown to occur in the constitutive, noninducble aP2-cre recombinase mouse line (Urs et al 2006;Martens et al 2010). Therefore, the aP2-Cre-ERT2 model enables uncoupling of adipocyte-intrinsic consequences of gene inactivation from that due to altered adipose tissue inflammation that occurs in response to nutritional overload (Imai et al 2001).…”