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ludc web

Cecilia Skoug

Doctoral student

ludc web

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

Author

  • Adélaïde A Mohr
  • Alba M Garcia-Serrano
  • João Pp Vieira
  • Cecilia Skoug
  • Henrik Davidsson
  • João MN Duarte

Summary, in English

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.

Department/s

  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Diabetes and Brain Function
  • WCMM-Wallenberg Centre for Molecular Medicine

Publishing year

2021-07-01

Language

English

Pages

1734-1743

Publication/Series

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism

Volume

41

Issue

7

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Physiology
  • Endocrinology and Diabetes

Status

Published

Research group

  • Diabetes and Brain Function

ISBN/ISSN/Other

  • ISSN: 1559-7016