Parabrachial Interleukin-6 Reduces Body Weight and Food Intake and Increases Thermogenesis to Regulate Energy Metabolism

Cell Rep. 2019 Mar 12;26(11):3011-3026.e5. doi: 10.1016/j.celrep.2019.02.044.

Abstract

Chronic low-grade inflammation and increased serum levels of the cytokine IL-6 accompany obesity. For brain-produced IL-6, the mechanisms by which it controls energy balance and its role in obesity remain unclear. Here, we show that brain-produced IL-6 is decreased in obese mice and rats in a neuroanatomically and sex-specific manner. Reduced IL-6 mRNA localized to lateral parabrachial nucleus (lPBN) astrocytes, microglia, and neurons, including paraventricular hypothalamus-innervating lPBN neurons. IL-6 microinjection into lPBN reduced food intake and increased brown adipose tissue (BAT) thermogenesis in male lean and obese rats by increasing thyroid and sympathetic outflow to BAT. Parabrachial IL-6 interacted with leptin to reduce feeding. siRNA-mediated reduction of lPBN IL-6 leads to increased weight gain and adiposity, reduced BAT thermogenesis, and increased food intake. Ambient cold exposure partly normalizes the obesity-induced suppression of lPBN IL-6. These results indicate that lPBN-produced IL-6 regulates feeding and metabolism and pinpoints (patho)physiological contexts interacting with lPBN IL-6.

Keywords: PVN; brown adipose tissue; cold exposure; diet-induced obesity; energy balance; hindbrain; lateral PBN; obesity; sex differences; thyroid.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Brown / metabolism
  • Animals
  • Astrocytes / metabolism
  • Body Weight*
  • Eating*
  • Energy Metabolism*
  • Female
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Leptin / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neurons / metabolism
  • Parabrachial Nucleus / metabolism*
  • Parabrachial Nucleus / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Sympathetic Nervous System / physiology
  • Thermogenesis*
  • Thyroid Hormones / metabolism

Substances

  • Interleukin-6
  • Leptin
  • Thyroid Hormones