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RESEARCH

Neurobiology of Obesity


The brain is a precise homeostat because it possesses tightly regulated pathways and mechanisms to ensure that internal conditions in the body remain within a healthy range. These conditions include energy and fluid balance, blood pressure, sleep pressure, and hormone levels that are highly interconnected and monitored to sustain health. In effect, any form of dyshomeostasis gives rise to a wide range of major health complications. Research in the Chee lab focuses on understanding how the brain controls metabolism – the body’s engine that converts food and drink into energy for growth, repair, and vital daily functions.

One major complication of metabolism is obesity, a complex metabolic disease that increases the risk of other fatal diseases like diabetes, cardiovascular disease, liver disease, and some cancers. Very few therapies have emerged to treat obesity, but this is unsurprising because we cannot fix a problem that we do not fully understand. In the brain, the hypothalamus is the most important region for homeostatic control. The Chee lab employs multiple approaches and techniques at the systems, circuit, and cellular level to understand the hypothalamic control of metabolic disease and obesity.


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Neural control of feeding

The brain controls what and how much we eat in accordance with calories burned to maintain stable body weight. The hypothalamus employs brainwide connections to coordinate food intake and feeding behavior, and it also responds to cues arising from peripheral organs that signal hunger or fullness.

The Chee lab investigates the circuits and mechanisms by which chemical messengers act in the brain to regulate hunger. These chemical messengers may be neuropeptides or classical neurotransmitters made within the brain; hormones released by the gut; or circulating factors released by organs like the pancreas or liver.

Selected publications

Payant MA, Spencer CD, Koziel Ly NK, Chee MJ (2024) Inhibitory actions of melanin-concentrating hormone in the lateral septum. J Physiol 602:3545 —3574.

Payant MA, Shankhatheertha A, Chee MJ (2024) Melanin-concentrating hormone promotes feeding through the lateral septum. Prog Neuropsychopharmacol Biol Psychiatry :111163 —https://doi.org/10.1016/j.pnpbp.2024.111163.

Sankhe AS, Bordeleau D, Alfonso DIM, Wittman G, Chee MJ (2023) Loss of glutamatergic signalling from MCH neurons reduced anxiety-like behaviours in novel environments. J Neuroendocrinol 35:e13222

Naganuma F, Bandaru SS, Absi G, Chee MJ, Vetrivelan R (2019) Melanin-concentrating hormone neurons promote rapid eye movement sleep independent of glutamate release. Brain Struct Funct 224:99 —110.

Neural control of feeding

The brain controls what and how much we eat in accordance with calories burned to maintain stable body weight. The hypothalamus employs brainwide connections to coordinate food intake and feeding behavior, and it also responds to cues arising from peripheral organs that signal hunger or fullness.

The Chee lab investigates the circuits and mechanisms by which chemical messengers act in the brain to regulate hunger. These chemical messengers may be neuropeptides or classical neurotransmitters made within the brain; hormones released by the gut; or circulating factors released by organs like the pancreas or liver.

Selected publications

Payant MA, Spencer CD, Koziel Ly NK, Chee MJ (2024) Inhibitory actions of melanin-concentrating hormone in the lateral septum. J Physiol 602:3545 —3574.

Payant MA, Shankhatheertha A, Chee MJ (2024) Melanin-concentrating hormone promotes feeding through the lateral septum. Prog Neuropsychopharmacol Biol Psychiatry :111163 —https://doi.org/10.1016/j.pnpbp.2024.111163.

Sankhe AS, Bordeleau D, Alfonso DIM, Wittman G, Chee MJ (2023) Loss of glutamatergic signalling from MCH neurons reduced anxiety-like behaviours in novel environments. J Neuroendocrinol 35:e13222

Naganuma F, Bandaru SS, Absi G, Chee MJ, Vetrivelan R (2019) Melanin-concentrating hormone neurons promote rapid eye movement sleep independent of glutamate release. Brain Struct Funct 224:99 —110.


Nutrients as neuromodulators

We are what we eat.
In addition to feeding our bodies, macronutrients like sugars, fats, and protein, impact brain health, brain function, as well as decision making about food.

The Chee lab investigates the impact of dietary fructose on obesity. Fructose is the sweetest of all simple sugars, and it is used excessively in sweetened drinks, ultra processed foods, and baked goods. We found that dietary fructose produces rapid changes favoring the excitation of neurons that drive feeding, and our current efforts are aimed at preventing fructose-induced maladaptations that tip the scale.

Selected publications:

Payant MA, Sankhe AS, Miller PA, Vieira SS, Dumiaty Y, Phy-Lim J, Levy ZL, Chee MJ (2025) Fructose-induced synaptic and neuronal adaptations at Neuropeptide Y/agouti-related peptide neurons. Mol Metab 99:102209

Chee MJ, Koziel Ly N, Anisman H, Matheson K (2020) Piece of cake: Coping with COVID-19 Nutrients 12:E3803
Nutrients as neuromodulators

We are what we eat. In addition to feeding our bodies, macronutrients like sugars, fats, and protein, impact brain health, brain function, as well as decision making about food.

The Chee lab investigates the impact of dietary fructose on obesity. Fructose is the sweetest of all simple sugars, and it is used excessively in sweetened drinks, ultra processed foods, and baked goods. We found that dietary fructose produces rapid changes favoring the excitation of neurons that drive feeding, and our current efforts are aimed at preventing fructose-induced maladaptations that tip the scale.

Selected publications:

Payant MA, Sankhe AS, Miller PA, Vieira SS, Dumiaty Y, Phy-Lim J, Levy ZL, Chee MJ (2025) Fructose-induced synaptic and neuronal adaptations at Neuropeptide Y/agouti-related peptide neurons. Mol Metab 99:102209

Chee MJ, Koziel Ly N, Anisman H, Matheson K (2020) Piece of cake: Coping with COVID-19 Nutrients 12:E3803










Hunger Takes It All: A powerful drive shaping our choices

Hunger is an emergency signal that prevents starvation and death, but it is only one of many signals necessary for survival. In addition to monitoring internal energy levels, living organisms are also on alert to avoid dangers in the external environment. Dangers may include exposure to anxiogenic stimuli, predators, or pain.

The Chee lab investigates the circuits and mechanisms allowing organisms to prioritize hunger over other survival pressures like the experience of pain or encounters with predators.

Selected publications

Phy-Lim J, Miller PA, Chee MJ (2025) Zona incerta suppressed escape during hunger. CUJS 5:1.

*Goldstein N, *Maes A, Allen HN, Nelson TS, Kruger KA, Kindel M, Yeung ATM, Smith NK, Carty JRE, Boccia L, Blank N, Lo E, Villari RE, Cho E, Marble EL, Awh M, Dumiaty Y, Chee MJ, Khanna R, Thaiss CA, Taylor BK, Kennedy A, Betley JN (2025) A parabrachial hub for need-state control of enduring pain. Nature : —https://doi.org/10.1038/s41586-025-09602.