Effects of Adipocyte-derived Factors on the Adrenal Cortex

Curr Mol Pharmacol. 2020;13(1):2-6. doi: 10.2174/1874467212666191015161334.

Abstract

Background and objective: Obesity is highly complicated by hypertension and hyperglycemia. In particular, it has been proposed that obesity-related hypertension is caused by adipocyte-derived factors that are recognized as undetermined proteins secreted from adipocytes. Adipocyte-derived factors have been known to be related to aldosterone secretion in the adrenal gland. So far, Wnt proteins, CTRP-1, VLDL, LDL, HDL and leptin have been demonstrated to stimulate aldosterone secretion. In contrast, it has not yet been clarified whether adipocyte-derived factors also affect adrenal cortisol secretion.

Methods and results: In the present study, we investigated the effect of adipocyte-derived factors on cortisol synthase gene CYP11B1 mRNA expression in vitro study using adrenocortical carcinoma H295R cells and mouse fibroblast 3T3-L1cells. Interestingly, adipocyte-derived factors were demonstrated to have the ability to stimulate CYP11B1 mRNA expression.

Conclusion: Since CYP11B1 is well known as a limiting enzyme of cortisol synthesis, our study suggests that adipocyte-derived factors may stimulate cortisol secretion, as well as aldosterone secretion. Taken together, adipocyte-derived factors may be the cause of metabolic syndrome due to their stimulating effects on aldosterone/cortisol secretion. Therefore, the innovation of novel drugs against them may possibly be a new approach against metabolic syndrome.

Keywords: CYP11B1; CYP11B2; Obesity; adipocyte; adrenal; cortisol..

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adipocytes / chemistry*
  • Adrenal Cortex / drug effects*
  • Adrenal Cortex / metabolism
  • Adrenal Cortex Neoplasms / metabolism
  • Adrenal Cortex Neoplasms / pathology
  • Animals
  • Carcinoma / metabolism
  • Carcinoma / pathology
  • Cell Line
  • Cell Line, Tumor
  • Cytochrome P-450 CYP11B2 / biosynthesis*
  • Cytochrome P-450 CYP11B2 / genetics
  • Fibroblasts
  • Gene Expression Regulation / drug effects
  • Humans
  • Hydrocortisone / metabolism
  • Leptin / metabolism
  • Leptin / pharmacology
  • Lipoproteins, LDL / metabolism
  • Lipoproteins, LDL / pharmacology
  • Mice
  • Proteins / genetics
  • Proteins / physiology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Steroid 11-beta-Hydroxylase / biosynthesis*
  • Steroid 11-beta-Hydroxylase / genetics
  • Wnt Proteins / metabolism
  • Wnt Proteins / pharmacology
  • Zona Fasciculata / drug effects
  • Zona Fasciculata / metabolism

Substances

  • C1QTNF1 protein, human
  • Leptin
  • Lipoproteins, LDL
  • Proteins
  • RNA, Messenger
  • Wnt Proteins
  • Cytochrome P-450 CYP11B2
  • Steroid 11-beta-Hydroxylase
  • Hydrocortisone