Chronic low-dose glucocorticoid treatment increases subcutaneous abdominal fat, but not visceral fat, of male Wistar rats

Life Sci. 2017 Dec 1:190:29-35. doi: 10.1016/j.lfs.2017.09.030. Epub 2017 Sep 25.

Abstract

Aim: Most studies developed to investigate the effects of glucocorticoids chronic treatment on white adipose tissue uses high doses of these hormones. This study analyzes some effects of a chronic, continuous and steady infusion of low-dose hydrocortisone and the relationship with lipid accumulation in white adipose depots in rats.

Main methods: Nineteen male Wistar rats were divided into control (CON) and cortisol (CORT) groups. Along six weeks CORT group received continuous infusion of 0.6mg/kg/day of hydrocortisone, while CON group received saline. After euthanasia, subcutaneous and visceral (retroperitoneal and mesenteric) fat pads were excised, weighted and analyzed for: lipogenic enzymes activity; molecular changes of 11-hydroxysteroid dehydrogenase type 1 (11βHSD1) enzyme; enzymes involved in lipid uptake, incorporation, and metabolism and in fatty acids esterification. Besides, morphometric cell analysis was performed.

Key findings: CORT group showed increased triglycerides, changes in lipoprotein profile and 26,8% increment in central subcutaneous (SC) mass, while visceral fat pads masses remained unchanged. Adipocytes from SC, only, presented increased fatty acid synthase, ATP-citrate lyase and glucose-6-phosphate dehydrogenase activity, in addition to reduced AMP-activated protein kinase and 11βHSD1 enzymes content.

Significance: Chronic low-dose hydrocortisone treatment consequences seem to be different from those commonly seen in long term hypercortisolism. While high doses promote lipid accumulation in visceral depots, a low dose showed an increase in central SC depot only. This appears to involve an increment in lipid storage and in de novo lipogenesis enzymes activity.

Keywords: Adipose tissue; Glucocorticoids; Lipogenesis; Low dose; Subcutaneous fat.

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism
  • Adipocytes / metabolism
  • Animals
  • Dose-Response Relationship, Drug
  • Fatty Acids / metabolism
  • Glucocorticoids / administration & dosage*
  • Glucocorticoids / pharmacology
  • Hydrocortisone / administration & dosage*
  • Hydrocortisone / pharmacology
  • Intra-Abdominal Fat / drug effects*
  • Lipid Metabolism
  • Lipogenesis
  • Male
  • Rats
  • Rats, Wistar
  • Subcutaneous Fat, Abdominal / drug effects*
  • Triglycerides / metabolism

Substances

  • Fatty Acids
  • Glucocorticoids
  • Triglycerides
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1
  • Hydrocortisone