Nitric Oxide and Thermogenic Function of Brown Adipose Tissue in Rats.

Abstract

Brown adipose tissue (BAT) is a thermogenic organ and its thermogenesis is indispensable when nonshivering thermogenesis is the main source of heat for body temperature regulation in mammals. Exposure of animals to a cold ambient temperature activates BAT, enhancing nonshivering thermogenesis to maintain a constant body temperature. Daily immobilization stress for several hours over several weeks in rats also activates the BAT function, and when these animals are exposed to a cold ambient temperature, they show an enhanced nonshivering thermogenic capacity, a phenomenon which is termed as cross adaptation [1][2][3][4]. Both cold exposure and repetitive immobilization stress may stimulate the sympathetic nervous system, initiating BAT activities responsible for the enhancement of nonshivering thermogenesis.Blood flow perfusing BAT determines the thermogenic activity of the tissue. When the rats are exposed to cold or injected with the sympathetic nerve transmitter noradrenaline, the tissue is perfused with more blood to meet the increased metabolic demand. This increase in BAT blood flow ceases if the rats are coinjected with N -nitro-L-arginine methyl ester (L-NAME; a nitric oxide synthase inhibitor), implying a role for nitric oxide (NO) in the regulation of BAT blood flow [5]. This finding justified further investigation to explore the role of NO in BAT nonshivering thermogenesis. Subsequently, we reported that chronic treatment with L-NAME decreases the nonshivering thermogenic capacity of rats. The L-NAME-treated rats develop hypothermia on acute exposure to a cold ambient temperature and do not show any response to noradrenaline that normally increases oxygen consumption in vivo [6]. The thermogenic capacity of BAT isolated from these rats, as estimated by DNA content and in vitro oxygen consumption, is also found to be suppressed. In these previous studies, we adopted pharmacological means to suppress the NO synthase, but did not show any firm evidence of NO synthesis in BAT. In addition, it is not known if the physiological conditions that are known to enhance adaptive thermogenesis would enhance the capacity for NO synthesis in BAT. In this study, therefore, we addressed the question of firm evidence of NO in BAT Japanese Journal of Physiology, 50, 337-342, 2000 Key words: brown adipose tissue, nitric oxide, in vitro oxygen consumption, nonshivering thermogenesis. Abstract:To clarify the effects of cold acclimation and immobilization stress adaptation of rats on nitric oxide (NO) activity in interscapular brown adipose tissue (BAT), we incubated neatly diced (1-mm 3 blocks) BAT in a metabolic chamber for respiration, measured oxygen consumption using a Clark electrode, and estimated NO release in the buffer medium by measuring nitrite plus nitrate (NO x ) using the Griess method (diazotization reaction). The production of NO x in the buffer medium confirmed that BAT releases NO, as there is no other source of NO x in the system. The NO activity was observed in the basal condition and increased with no...

Thermoregulatory role of inducible nitric oxide synthase in lipopolysaccharide-induced hypothermia

“…However, NO has been demonstrated as an important element in body temperature control during basal and infectious situations (Gerstberger, 1999;Steiner and Branco, 2001). Many works supported the hypothesis that NO has a pyretic role during fever (Kamerman et al, 2002;Kozak and Kozak, 2003), acting in brown adipose tissue, facilitating the thermogenic production (Saha et al, 1996;Saha and Kuroshima, 2000). On the other hand, it has been speculated that NO had an antipyretic role in the central nervous system (CNS), since intracerebroventricular administration of NO donors reduced fever in rabbits (Gourine, 1995).…”

The effects of l-arginine and l-NAME supplementation on redox-regulation and thermogenesis in interscapular brown adipose tissue

“…It has been shown that brown adipocytes express the eNOS (Giordano et all., 2002) and iNOS (Nisoli et al, 1997) and that NO produced by these isoforms is involved in regulation of BAT function (Kikuchi-Utsumi et al, 2002;Nisoli et al, 1997Nisoli et al, , 2003. Recent findings justified the role of NO in BAT nonshivering thermogenesis (Saha and Kuroshima, 2000). It can mediate increased blood flow to BAT following noradrenergic stimulation (Nagashima et al, 1994;KikuchiUtsumi et al, 2002) and take part in differentiation and proliferation (Nisoli et al, 1998) in brown adipocyte cultures.…”

Supplementation of Fruit Extract of Hippophae rhamnoides Speeds Adaptation to Simulated High Altitude Stressors in Rats

“…This observed decrease in oxidative stress was due to the anti-oxidant effect of the extract which has high content of ascorbic acid and shown the presence of complex flavonoid composition including isorhamnetin, quercetin, kaempferol and glycosides (Chen 1990;Yao 1992;Yang 2001;Barl 2003). In this study, NO, a potent vasodilator, involved in the enhancement of the thermogenic function of brown adipose tissue (Saha and Kuroshima 2000), did not reveal any change in extract treated rats exposed to C-H-R stress.…”