A new mouse model for noninvasive fluorescence‐based monitoring of mitochondrial UCP1 expression

Abstract

Mitochondrial uncoupling protein 1 (UCP1) is well known for its thermogenic function in brown adipose tissue (BAT). Since UCP1 expends energy on thermogenesis, UCP1 activation has been considered an approach to ameliorate obesity. As a tool for uncovering yet unknown mechanisms of UCP1 activation, we generated a transgenic mouse model in which UCP1 expression levels are reflected in fluorescence derived from monomeric red fluorescent protein 1 (mRFP1). In these UCP1‐mRFP1 BAC transgenic mice, fluorescence intensity mimics the change in UCP1 expression levels evoked through physiological or pharmacological stimulation. This transgenic mouse model will be useful in the search for bioactive compounds with the ability to induce UCP1 and for revealing undiscovered mechanisms of BAT activation.

Involvement of mechano-sensitive Piezo1 channel in the differentiation of brown adipocytes

“…Male C57Bl/6NCr mice (SLC, Hamamatsu, Japan) and UCP1-mRFP1 transgenic mice [30] were housed in a controlled environment (12-h light/dark cycle; 22-24 °C; 50-60% humidity) with food and water provided ad libitum. All animal protocols were approved by the animal research committees of University of Shizuoka (Shizuoka, Japan) and Kyoto University (Kyoto, Japan), and were performed in accordance with institutional guidelines.…”

“…We used immortalized pre-adipocytes isolated from interscapular BAT (iBAT) of UCP1-mRFP1 transgenic mice [30]. Immortalized pre-adipocytes were cultured in standard medium containing FBS, glutamine, and penicillin/streptomycin in DMEM.…”

“…In this study, we generated a brown adipocyte line from UCP1-mRFP1 transgenic mice [30] and found the expression of Piezo1 in brown adipocytes. Furthermore, we observed the effect of a Piezo1 agonist on the differentiation of brown adipocytes and analyzed the effect of Piezo1 knockdown (KD) in brown adipocytes.…”

<p>Comparative Analysis of the Preventive Effects of Canagliflozin, a Sodium-Glucose Co-Transporter-2 Inhibitor, on Body Weight Gain Between Oral Gavage and Dietary Administration by Focusing on Fatty Acid Metabolism</p>

“…Total RNA extraction, reverse transcription and quantitative polymerase chain reaction were performed as described previously. 12 All oligonucleotide primer sets used were designed as previously reported. 10,13 All mRNA expression data were normalized to the expression of 36b4.…”

Physiological Implications of Orexins/Hypocretins on Energy Metabolism and Adipose Tissue Development

“…As is well known, two types of adipose tissuewhite adipose tissue (WAT) and BATexist in mammals . WAT is mainly responsible for metabolic energy storage, whereas BAT maintains body temperature through its thermogenic activity, by dissipating energy . Orexin-A knockout mice show late-onset obesity despite no significant change in food intake .…”