Thermogenic recruitment of brown and brite/beige adipose tissues is not obligatorily associated with macrophage accretion or attrition

Am J Physiol Endocrinol Metab. 2021 Feb 1;320(2):E359-E378. doi: 10.1152/ajpendo.00352.2020. Epub 2020 Dec 7.

Abstract

Cold- and diet-induced recruitment of brown adipose tissue (BAT) and the browning of white adipose tissue (WAT) are dynamic processes, and the recruited state attained is a state of dynamic equilibrium, demanding continuous stimulation to be maintained. An involvement of macrophages, classical proinflammatory (M1) or alternatively activated anti-inflammatory (M2), is presently discussed as being an integral part of these processes. If these macrophages play a mediatory role in the recruitment process, such an involvement would have to be maintained in the recruited state. We have, therefore, investigated whether the recruited state of these tissues is associated with macrophage accretion or attrition. We found no correlation (positive or negative) between total UCP1 mRNA levels (as a measure of recruitment) and proinflammatory macrophages in any adipose depot. We found that in young chow-fed mice, cold-induced recruitment correlated with accretion of anti-inflammatory macrophages; however, such a correlation was not seen when cold-induced recruitment was studied in diet-induced obese mice. Furthermore, the anti-inflammatory macrophage accretion was mediated via β12-adrenergic receptors; yet, in their absence, and thus in the absence of macrophage accretion, recruitment proceeded normally. We thus conclude that the classical recruited state in BAT and inguinal (brite/beige) WAT is not paralleled by macrophage accretion or attrition. Our results make mediatory roles for macrophages in the recruitment process less likely.NEW & NOTEWORTHY A regulatory or mediatory role-positive or negative-for macrophages in the recruitment of brown adipose tissue is presently discussed. As the recruited state in the tissue is a dynamic process, maintenance of the recruited state would need persistent alterations in macrophage complement. Contrary to this expectation, we demonstrate here an absence of alterations in macrophage complement in thermogenically recruited brown-or brite/beige-adipose tissues. Macrophage regulation of thermogenic capacity is thus less likely.

Keywords: brown adipose tissue; cold; macrophages; obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Beige / cytology
  • Adipose Tissue, Beige / physiology*
  • Adipose Tissue, Brown / cytology
  • Adipose Tissue, Brown / physiology*
  • Animals
  • Diet / adverse effects
  • Gene Expression Regulation
  • Macrophages / cytology
  • Macrophages / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / etiology
  • Obesity / metabolism
  • Obesity / pathology
  • Receptors, Adrenergic, beta-1 / physiology*
  • Receptors, Adrenergic, beta-2 / physiology*
  • Thermogenesis*
  • Uncoupling Protein 1 / genetics
  • Uncoupling Protein 1 / metabolism

Substances

  • ADRB2 protein, mouse
  • Adrb1 protein, mouse
  • Receptors, Adrenergic, beta-1
  • Receptors, Adrenergic, beta-2
  • Ucp1 protein, mouse
  • Uncoupling Protein 1