Nanolive imaging confirms norepinephrine triggers lipid accumulation in pre-adipocyte cells

Norepinephrine: a vital modulator of blood pressure, blood sugar, and fat levels in the body

Norepinephrine (also known as noradrenaline or noradrenalin) is an organic catecholamine that acts as the main neurotransmitter in the sympathetic cardiovascular system. Naturally synthesized in the adrenal medulla and postganglion neurons of the nervous system, norepinephrine plays an important role in regulating blood pressure, blood sugar levels, and fat breakdown. It is also an important injectable drug for the treatment of low blood pressure.

Norepinephrine’s mechanism of action: focus on lipolysis

Like other catecholamines, norepinephrine is mediated by adrenoreceptors (ARs). Three classes of ARs exist (α1, α2 and β), each of which mediate a variety of functions depending on their localization in the body [1]. One of the most important roles that ARs play is in the control of lipolysis (fat reserves) in adipocyte cells, which depends on the functional balance of between stimulatory (β1-, β2-, and β3) and inhibitory (α2) ARs [1].

Investigating how norepinephrine influences cell morphology using Nanolive label-free live cell imaging

In this video, 3T3-derived pre-adipocyte cells were incubated with norepinephrine and imaged after 45 mins, 4 h 30 mins, and 48 h. One image was captured every 6 seconds for 10-15 mins using Nanolive’s 3D Cell Explorer-fluo. The cell exposed to norepinephrine for 48 h has a markedly different morphology compared to cells at the earlier time points. There is a clear accumulation of lipid droplets (LDs; the bright spheres) around the periphery of the nucleus, compared to cells at earlier time-points. Time-dependent responses to norepinephrine exposure were also observed in brown adipocytes cells, where 5 d were required to observe changes in lipid deposits [2].

How can Nanolive imaging contribute to future research on the effects of norepinephrine?

It is worth pointing out that in this example we use preadipocyte cells, where the inhibitory α2-AR is the highest AR subtype expressed, in contrast to mature adipocyte cells, where stimulatory β3-ARs dominate [3]. Comparing preadipocytes and adipocytes responses to norepinephrine could shed light on the role catecholamines play in cell differentiation.

As Nanolive imaging is label-free, cells can be monitored over long time periods, making it possible to examine the role of catecholamines in population growth. Proliferation in pre-adipocytes is controlled in part by α2-AR activation through the mitogen-activated protein kinase (MAP) kinase pathway [4], which is directly stimulated by norepinephrine, so it might be interesting to compare the effect different concentrations of norepinephrine have on division rates, while perturbing the MAP kinase pathway.

Nanolive imaging is compatible with a huge variety of cells, so it would also be interesting to examine the effects of norepinephrine on different cell types, neurons in particular.

To learn how Nanolive imaging can be used to study cell metabolism, specifically mitochondria and lipid droplets morphology and dynamics, visit our dedicated application page here.

References

[1] Robidoux J, Martin TL, Collins S. β-adrenergic receptors and regulation of energy expenditure: a family affair. Annual Review Pharmacology and Toxicology. 2004 Feb 10;44:297-323.

[2] Cinti S, Cigolini M, Sbarbati A, Zancanaro C, Björntorp P. Effects of noradrenaline exposure on rat brown adipocytes in cultures. An ultrastructural study. Tissue and Cell. 1987 Jan 1;19(6):809-15.

[3] Monjo M, Pujol E, Roca P. α2-to β3-Adrenoceptor switch in 3T3-L1 preadipocytes and adipocytes: modulation by testosterone, 17β-estradiol, and progesterone. American Journal of Physiology-Endocrinology and Metabolism. 2005 Jul;289(1):E145-50.

[4] Bouloumie A, Planat V, Devedjian JC, Valet P, Saulnier-Blache JS, Record M, Lafontan M. Alpha 2-adrenergic stimulation promotes preadipocyte proliferation. Involvement of mitogen-activated protein kinases. Journal of Biological Chemistry. 1994 Dec 2;269(48):30254-9.

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