A glucose-stimulated BOLD fMRI study of hypothalamic dysfunction in mice fed a high-fat and high-sucrose diet

J Cereb Blood Flow Metab. 2021 Jul;41(7):1734-1743. doi: 10.1177/0271678X20942397. Epub 2020 Aug 5.

Abstract

The hypothalamus is the central regulator of energy homeostasis. Hypothalamic neuronal circuits are disrupted upon overfeeding, and play a role in the development of metabolic disorders. While mouse models have been extensively employed for understanding the mechanisms of hypothalamic dysfunction, functional magnetic resonance imaging (fMRI) on hypothalamic nuclei has been challenging. We implemented a robust glucose-induced fMRI paradigm that allows to repeatedly investigate hypothalamic responses to glucose. This approach was used to test the hypothesis that hypothalamic nuclei functioning is impaired in mice exposed to a high-fat and high-sucrose diet (HFHSD) for seven days. The blood oxygen level-dependent (BOLD) fMRI signal was measured from brains of mice under light isoflurane anaesthesia, during which a 2.6 g/kg glucose load was administered. The mouse hypothalamus responded to glucose but not saline administration with a biphasic BOLD fMRI signal reduction. Relative to controls, HFHSD-fed mice showed attenuated or blunted responses in arcuate nucleus, lateral hypothalamus, ventromedial nucleus and dorsomedial nucleus, but not in paraventricular nucleus. In sum, we have developed an fMRI paradigm that is able to determine dysfunction of glucose-sensing neuronal circuits within the mouse hypothalamus in a non-invasive manner.

Keywords: Glucose sensing; diet-induced obesity; functional imaging; hypothalamus; neuronal stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diet, High-Fat*
  • Dietary Sucrose / toxicity*
  • Glucose / administration & dosage*
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Hypothalamus / pathology*
  • Magnetic Resonance Imaging / methods*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / physiopathology*

Substances

  • Dietary Sucrose
  • Glucose