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Brain nutrient sensing and energy homeostasis


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Researchers

M-C. Brindisi, L. Brondel, A. Jacquin Piques.

Enginneers and technicians

S. Barthet, C. Forbes Fenech, S. Grall, F. Liénard.

Post-docs

B. Abed.

The main focus of our research is to define the mechanisms and understand the role of the cerebral nutrient detection, especially that of glucose. Blood glucose levels, body weight and fat content are maintained in a steady state throughout the life in adults. Thus, nervous and circulating factors continuously inform the brain about energy status. Among these factors, glucose is an essential signal to sensory and specific brain structures. Glucose is detected at two main sites: the digestive tract and the hypothalamus. This detection activates some neuronal circuits involved in the control of food intake, preferences, and metabolism. In metabolic pathologies, this nutrient sensing is altered: it is therefore crucial to understand the mechanisms underlying how the brain senses and perceives nutrients, especially glucose, to define new strategies to fight obesity and diabetes type 2, among some others.

Key words : Brain glucose sensing, hypothalamus, sweet taste detection and perception, neurons and astrocytes, ionic channels, mitochondria, metabolic pathologies (obesity, diabetes, hepatic and renal failures), food intake/behavior, metabolism.

Thematic : Control of food intake and energy metabolism
Molecular, cellular and integrated approaches to study the mechanisms that link brain nutrient sensing with the control of energy balance (food intake and metabolism), under physiological and pathological conditions in both human and animal models.

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Theme 1 :

1) The identification of cellular and molecular actors of hypothalamic nutrient sensing and their importance in energy homeostasis

Theme 2 :

2) The understanding of how energy status under both physiological and pathological conditions alters hypothalamic nutrient detection and gustative perception. Researches are conducted by exploring the control of food intake, preferences and metabolism in human beings. Cellular and molecular hypothalamic modifications/dysregulations are examined in depth using appropriate animal models.

  •  Rodent
  •  Human model
  •  In vitro

ANR Fat4brain 2017-2021

AFERO prize 2016: Physiological mechanisms involved in fat taste and perception in Humans.

Prize of French Society of Nutrition 2015: Brain control of food intake through gustative-evoked potentials studies in obese people: correlations with plasmatic leptin, ghrelin, insulin and dopamine levels.

BQR 2015 (financial support from the University of Burgundy): Mitochondrial redox signaling and cardio-metabolic risks associated to nutritional changes during the perinatal period.

Prize of the French Society of Diabetes 2015: Comparative study (from 3 to 9 months) of the food behavior of obese people with a type 2 diabetes treated with SGLT2 inhibitors.

ANR Connexsensing (2011-2015, financial support from the French Agency for Research): Role of astroglial connexins in hypothalamic glucose detection: implication in the nervous control of the metabolism.

IndustriaI Servier's contract (2014-15): Effect of a high fat diet-induced desynchronization on circadian rythms of insulin secretion: role of reverba and pharmacologic modulators.

Transient Receptor Potential Canonical 3 (TRPC3) Channels Are Required for Hypothalamic Glucose Detection and Energy Homeostasis. Chrétien C, Fenech C, Liénard F, Grall S, Chevalier C, Chaudy S, Brenachot X, Berges R, Louche K, Stark R, Nédélec E, Laderrière A, Andrews ZB, Benani A, Flockerzi V, Gascuel J, Hartmann J, Moro C, Birnbaumer L, Leloup C, Pénicaud L, Fioramonti X. Diabetes. 2017,66(2):314-324.

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Glucose and hypothalamic astrocytes: More than a fueling role? Leloup C, Allard C, Carneiro L, Fioramonti X, Collins S, Pénicaud L. Neuroscience. 2016, 323:110-20.

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Preference for Sucrose Solutions Modulates Taste Cortical Activity in Humans. Jacquin-Piques A, Mouillot T, Gigot V, Meillon S, Leloup C, Penicaud L, Brondel L. Chem Senses. 2016, 41(7):591-9.

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Hypothalamic sensing of ketone bodies after prolonged cerebral exposure leads to metabolic control dysregulation. Carneiro L, Geller S, Hébert A, Repond C, Fioramonti X, Leloup C, Pellerin L. Sci Rep. 2016, 6:34909.

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Prandial States Modify the Reactivity of the Gustatory Cortex Using Gustatory Evoked Potentials in Humans. Jacquin-Piques A, Gaudillat S, Mouillot T, Gigot V, Meillon S, Leloup C, Penicaud L, Brondel L. Front Neurosci. 2016, 9:490.

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Hypothalamic astroglial connexins are required for brain glucose sensing-induced insulin secretion. Allard C, Carneiro L, Grall S, Cline BH, Fioramonti X, Chrétien C, Baba-Aissa F, Giaume C, Pénicaud L, Leloup C. J Cereb Blood Flow Metab. 2014, 34(2):339-46

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Hypothalamic S-nitrosylation contributes to the counter-regulatory response impairment following recurrent hypoglycemia. Fioramonti X, Deak A, Deshpande S, Carneiro L, Zhou C, Sayed N, Orban B, Berlin JR, Pénicaud L, Leloup C, Beuve A, Routh VH. PLoS One. 2013, 8(7):e68709.

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Alteration of hypothalamic glucose and lactate sensing in 48h hyperglycemic rats. Allard C, Carneiro L, Collins SC, Chrétien C, Grall S, Pénicaud L, Leloup C. Neurosci Lett. 2013, 534:75-9.

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Importance of mitochondrial dynamin-related protein 1 in hypothalamic glucose sensitivity in rats. Carneiro L, Allard C, Guissard C, Fioramonti X, Tourrel-Cuzin C, Bailbé D, Barreau C, Offer G, Nédelec E, Salin B, Rigoulet M, Belenguer P, Pénicaud L, Leloup C. Antioxid Redox Signal. 2012, 17(3):433-44.

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  • AFERO
  • Société francophone du diabète
  • SFN
  • FEDER
  • Institut de France
  • Région Bourgogne
  • ANR