Modulation by insulin and glucagon of noradrenaline-induced activation of isolated brown adipocytes from the rat

Abstract

1. The effects of insulin (2 nM and 4 nM) upon oxygen consumption ( VoJ, lipolysis rates and indirectly derived rates of fatty acid utilization, by isolated brown adipocytes from warm-acclimated (W cells) and cold-acclimated (C cells) animals, induced by noradrenaline and glucagon separately and conjointly, are reported.2. Changes in interrelationships (coupling) between the parameters under different treatment regimes were assessed using bivariate regression analyses.3. Administration of glucagon with noradrenaline increased lipolysis/fatty acid utilization coupling without concomitant increase of Vo2 suggesting that glucagon may increase re-esterification through glycogenolytic generation of glycerol 3-phosphate, trapping intracellular fatty acid in excess of the capacity of disposal mechanisms, thus conserving respiratory substrate.4. W cells were unresponsive to glucagon in terms of lipolysis and po2'; C cells responded to glucagon with parallel increases in lipolysis rate and Both cell types responded to noradrenaline alone and conjointly with glucagon; C cells-were more sensitive to these agonists than W cells.5. Lipolysis/ Vo, coupling was reduced in C cells suggesting that in cold acclimation, noradrenaline-induced lipolysis rates are in excess of the capacity of cellular oxidation/re-esterification mechanisms.6. Insulin inhibited noradrenaline and glucagon-induced lipolysis, simultaneously increasing po2, supporting the hypothesis that glucose may be a thermogenic substrate in brown adipase tissue, permitting concurrent thermogenesis and lipogenesis. C cells were more insulin-sensitive than W cells.7. The data indicate that insulin may mediate its effects (additively with noradrenaline) by activation of pyruvate dehydrogenase, generating glycolytic flux and, in the presence of noradrenaline-inhibited lipogenesis, generate additional oxaloacetate, permitting increased P-oxidation.In homeotherms, non-shivering thermogenesis is mediated primarily by brown adipose tissue (BAT) [l]. The principal mechanism of activation is by means of increased sympathetic activity with liberation of noradrenaline from the dense adrenergic terminals with which the tissue is invested, and consequent activation of P-adrenergically mediated lipolysis leading to the liberation of free fatty acids from intracellular triacylglycerols. Subsequent P-oxidation of free fatty acids, associated with increased mitochondrial proton conductance induced by increased free fatty acid concentrations [2], leads to enhanced heat production by dissipation of the mitochondrial proton gradient [3]. A second effect attributed to noradrenaline release in chronic cold exposure is increased synthesis of mitochondrial protonophore [4].While noradrenaline appears to be the prime mediator of BAT thermogenesis [5], there is evidence that non-adrenergic factors such as glucagon [6, 71 may have permissive or

Metabolic cold acclimation after repetitive intermittent cold exposure in rat.

“…The increase of BAT weight did not differ between ICE and CA, although the increases in fat-free dry matter fraction and glucagon level of BAT were smaller in ICE than in CA. A possible role of glucagon in metabolic cold acclimation has been recently reported from our laboratory (KuROsHIMA et al, 1978(KuROsHIMA et al, , 1984(KuROsHIMA et al, , 1988 and also others (BILLINGTON et al, 1987;HOWLAND and BOND, 1987). The present study confirmed the previous results that glucagon level was higher in BAT from CA even in the resting state (HABARA and KUROSHIMA, 1983;, suggesting that glucagon exerts its thermogenic effect on BAT in high concentration.…”

Impact of Maternal Food Restriction on Cold-Induced Thermogenesis in the Offspring

“…BAT is the main effector of NST and is regulated mainly by sympathetic noradrenaline [33]. In vitro and in vivo experiments have shown that BAT function is also regulated by different hormonal factors such as thyroidal, adrenocortical and pancreatic hormones [34,35].…”

The Growth of Brown Adipose Tissue in Cold-acclimatized Rats after Depletion of Mast Cell Histamine by Compound 48/80

“…In control rats maintained at room temperature (28 ± 2°C) the BAT histamine content was 23.4 ± 5.9 (mean ± SD) Homeothermic animals have the capacity to maintain body temperature by a variety of physiological responses, the most important of which is to enhance nonshivering thermogenesis (NST). The rapid growth of the brown adipose tissue (BAT) appears to play a crucial role in NST and is thought to be mainly regulated by sympathetic noradrenaline (Rothwell & Stock 1985, Géloën et al 1992 as well as other hormonal factors like thyroidal, adrenocortical and pancreatic hormones (Kuroshima et al 1984, Howland & Bond 1987.…”

“…The rapid growth of the brown adipose tissue (BAT) appears to play a crucial role in NST and is thought to be mainly regulated by sympathetic noradrenaline (Rothwell & Stock 1985, Géloën et al 1992 as well as other hormonal factors like thyroidal, adrenocortical and pancreatic hormones (Kuroshima et al 1984, Howland & Bond 1987.…”

“…In control rats maintained at room temperature (28 ± 2°C) the BAT histamine content was 23.4 ± 5.9 (mean ± SD) Homeothermic animals have the capacity to maintain body temperature by a variety of physiological responses, the most important of which is to enhance nonshivering thermogenesis (NST). The rapid growth of the brown adipose tissue (BAT) appears to play a crucial role in NST and is thought to be mainly regulated by sympathetic noradrenaline (Rothwell & Stock 1985, Géloën et al 1992 as well as other hormonal factors like thyroidal, adrenocortical and pancreatic hormones (Kuroshima et al 1984, Howland & Bond 1987.Neurotransmitters that promote cell proliferation may do so by inhibiting adenylcyclase or by activating phospholipase C (PLC); these include 5-HT, adenosine (A1 receptors), norepinephrine (alpha-adrenergic receptors) and acetylcholine (muscarinic receptors) (for review see Lauder 1993). There are several reports that elevated level of histamine and its synthesizing enzyme are associated with rapid tissue growth (Kahlson & Rosengren 1968 Although the role of histamine in thermoregulation in the mammalian brain has been the focus of a number of investigations (Schwartz et al 1991), no data exist in relation to the possible participation of histamine in promoting the hyperplasia of BAT in nonhibernating mammals submitted to acclimatization.…”