Brown adipose tissue and its modulation by a mitochondria-targeted peptide in rat burn injury-induced hypermetabolism

Abstract

Hypermetabolism is a prominent feature of burn injury, and altered mitochondria function is presumed to contribute to this state. Recently, brown adipose tissue (BAT) was found to be present not only in rodents but also in humans, and its activity is associated with resting metabolic rate. In this report, we elucidate the relationship between burn injury-induced hypermetabolism and BAT activity and the possible role of the mitochondria-targeted peptide SS31 in attenuating burn injury-induced hypermetabolism by using a rat burn injury model. We demonstrate that burn injury induces morphological changes in interscapular BAT (iBAT). Burn injury was associated with iBAT activation, and this effect was positively correlated with increased energy expenditure. BAT activation was associated with augmentation of mitochondria biogenesis, and UCP1 expression in the isolated iBAT mitochondria. In addition, the mitochondria-targeted peptide SS31 attenuated burn injury-induced hypermetabolism, which was accompanied by suppression of UCP1 expression in isolated mitochondria. Our results suggest that BAT plays an important role in burn injury-induced hypermetabolism through its morphological changes and expression of UCP1.

Browning of Subcutaneous White Adipose Tissue in Humans after Severe Adrenergic Stress

“…2A), suggesting UCP1 transcription in sWAT in response to burn injury. These human data are in agreement with those from rodent models of burns, where UCP1 expression is induced in BAT and sWAT depots following burn trauma (Yo et al, 2012; Zhang et al, 2008). While data presented in Fig 2A were from cohorts of burn victims, we saw similar induction of UCP1 in a sub-group of burn victims followed prospectively after injury (P<0.01, Fig.…”

Dissociated Oxygen Consumption and Carbon Dioxide Production in the Post–Cardiac Arrest Rat: A Novel Metabolic Phenotype

“…In that article, nearly 25% of collected data were excluded from analysis because the measured RQ was <0.6 or >1.2. An increase in the metabolic rate, eg, hypermetabolism, has been reported in patients with burns,35, 36 sepsis,37 and other diseases 38, 39. However, these reports did not include measurements of VCO 2 and therefore it is possible that a shift in O 2 metabolism, such as the one described here, was interpreted as hypermetabolism.…”

Energy Metabolism in Burn Injury and Current Approaches to Determine the Energy Requirements

“…11,13 Yaklaşık olarak yanık sonrası beşinci gün baş-layıp 24 aya kadar sürebilen hipermetabolik yanı-tın birincil mediyatörleri, yaralanmadan sonra düzeyleri 10-15 kat artış gösteren proinflamatuar sitokinler, kortikosteroidler ve endojen plazma katekolaminlerdir. 9,16,17 Hasarlı dokulardan salı-nan sitokinler modifiye bazal metabolizmaya dö-nüşmekte ve akut travma sonrası uzun süre değişmiş olarak muhafaza edilmektedir. 2 Yanık sonrası hipermetabolik yanıt, hastanede kalış süre-since devam etmekte ve altı aydan uzun sürebil-mektedir.…”

“…6,14,16,19 Ayrıca, enerji substratlarının yoğun kullanımı hastada bağışıklık sistemi yetersizliği, enfeksiyonlar, önemli azot kaybı, gecikmiş yara iyileşmesi, çoklu organ yetmezliği, uzun süreli hastanede kalış ve mortaliteye neden olabilen malnütrisyona yol aç-maktadır. 4,17,20,21 Protein katabolizması, ağrı, ateş, mekanik ventilasyon, kortikosteroidler, vazoaktif ajanlar ve yara boyutu enerji tüketiminin artışına sebep olur iken; malnütrisyon, nöromusküler ajanlar enerji tüketi-mini azaltabilmektedir. 22 Yanık kaynaklı hipermetabolizmada REE; artan kalp hızı, solunum hızı, vücut ısısı, oksijen (O 2 ) tüketimi, karbondioksit (CO 2 ) üretimi, glukoz kullanımı, glukojenoliz, lipoliz ve proteoliz nedeni ile normal düzeyden iki kat yükselebilmektedir.…”