Hypothalamic dopamine signalling regulates brown fat thermogenesis

Folgueira, Cintia; Beiroa, Daniel; Porteiro, Begoña; Duquenne, Manon; Puighermanal, Emma; Fondevila, Marcos F.; Barja-Fernández, Silvia; Gallego, Rosalı́a; Hernández-Bautista, René; Castelao, Cecilia; Senra, Ana; Seoane-Collazo, Patricia; Gómez-Lado, Noemí; Aguiar, Pablo; Guallar, Diana; Fidalgo, Miguel; Romero‐Picó, Amparo; Adan, Roger A.H.; Blouet, Clémence; Labandeira-Garcı́a, José Luis; Jeanrenaud, F. Rohner; Kalló, Imre; Liposits, Zsolt; Salvador, Javier; Prévot, Vincent; Diéguez, Carlos; López, Miguel; Valjent, Emmanuel; Frühbeck, Gema; Seoane, Luísa M.; Nogueiras, Rubén

doi:10.1038/s42255-019-0099-7

Cited by 57 publications

(59 citation statements)

References 99 publications

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“…The lack of effects of the D2-agonist on iBAT thermogenesis shown in our study seemingly contradicts a recent study, where hypothalamic D2-agonist administration decreased body weight and stimulated iBAT activity in rodents 55 . However, in this study the effects of the D2-agonist were demonstrated to be mediated via centrally initiated activation of the sympathetic nervous system.…”

Section: Discussioncontrasting

confidence: 99%

Dopamine receptor D1- and D2-agonists do not spark brown adipose tissue thermogenesis in mice

Raffaelli

Resch

Oelkrug

et al. 2020

Sci Rep

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Brown adipose tissue (BAT) thermogenesis is considered a potential target for treatment of obesity and diabetes. In vitro data suggest dopamine receptor signaling as a promising approach; however, the biological relevance of dopamine receptors in the direct activation of BAT thermogenesis in vivo remains unclear. We investigated BAT thermogenesis in vivo in mice using peripheral administration of D1-agonist SKF38393 or D2-agonist Sumanirole, infrared thermography, and in-depth molecular analyses of potential target tissues; and ex vivo in BAT explants to identify direct effects on key thermogenic markers. Acute in vivo treatment with the D1- or D2-agonist caused a short spike or brief decrease in BAT temperature, respectively. However, repeated daily administration did not induce lasting effects on BAT thermogenesis. Likewise, neither agonist directly affected Ucp1 or Dio2 mRNA expression in BAT explants. Taken together, the investigated agonists do not seem to exert lasting and physiologically relevant effects on BAT thermogenesis after peripheral administration, demonstrating that D1- and D2-receptors in iBAT are unlikely to constitute targets for obesity treatment via BAT activation.

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Section: Discussioncontrasting

confidence: 99%

Dopamine receptor D1- and D2-agonists do not spark brown adipose tissue thermogenesis in mice

Raffaelli

Resch

Oelkrug

et al. 2020

Sci Rep

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“…Such adaptations to caloric restriction presumably arise to promote physical activity required to forage for food to obtain needed calories (26), making them potential therapeutic targets for reducing hyperactivity in AN. Dopamine also contributes to thermoregulation (95)(96)(97), which is altered in AN (6,98) and ABA (94,99). Hypothermia arising from weight loss may also induce changes in dopamine.…”

Section: Dopamine and An Vulnerabilitymentioning

confidence: 99%

Vulnerable and Resilient Phenotypes in a Mouse Model of Anorexia Nervosa

Beeler

Mourra

Zanca

et al. 2021

Biological Psychiatry

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BACKGROUND: Increased physical activity is a common feature of anorexia nervosa (AN). Although high activity levels are associated with greater risk of developing AN, particularly when combined with dieting, most individuals who diet and exercise maintain a healthy body weight. It is unclear why some individuals develop AN while most do not. A rodent model of resilience and vulnerability to AN would be valuable to research. Dopamine, which is believed to play a crucial role in AN, regulates both reward and activity and may modulate vulnerability. METHODS: Adolescent and young adult female C57BL/6N mice were tested in the activity-based anorexia (ABA) model, with an extended period of food restriction in adult mice. ABA was also tested in dopamine transporter knockdown mice and wild-type littermates. Mice that adapted to conditions and maintained a stable body weight were characterized as resilient. RESULTS: In adults, vulnerable and resilient phenotypes emerged in both the ABA and food-restricted mice without wheels. Vulnerable mice exhibited a pronounced increase in running throughout the light cycle, which dramatically peaked prior to requiring removal from the experiment. Resilient mice exhibited an adaptive decrease in total running, appropriate food anticipatory activity, and increased consumption, thereby achieving stable body weight. Hyperdopaminergia accelerated progression of the vulnerable phenotype. CONCLUSIONS: Our demonstration of distinct resilient and vulnerable phenotypes in mouse ABA significantly advances the utility of the model for identifying genes and neural substrates mediating AN risk and resilience. Modulation of dopamine may play a central role in the underlying circuit.

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“…The dopamine receptor 2 on GABAergic neurons in the LHA and zona incerta appears to be able to upregulate Ucp1, BAT thermogenesis, and energy expenditure in mice. This pathway is dependent on orexin signaling (117). The fact that dopamine plays a role in the orexigenic thermogenesis was reported before, when ablating the dopamine neurons resulted in abolishment of the orexigenic increase in body temperature (98).…”

Section: Neuroendocrine Pathways Involved In Orexigenic Thermoregulationmentioning

confidence: 61%

Role of Brown Adipose Tissue in Adiposity Associated With Narcolepsy Type 1

et al. 2020

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Narcolepsy type 1 is a neurological sleep-wake disorder caused by the destruction of orexin (hypocretin)-producing neurons. These neurons are particularly located in the lateral hypothalamus and have widespread projections throughout the brain, where they are involved, e.g., in the regulation of the sleep-wake cycle and appetite. Interestingly, a higher prevalence of obesity has been reported in patients with narcolepsy type 1 compared to healthy controls, despite a normal to decreased food intake and comparable physical activity. This suggests the involvement of tissues implicated in total energy expenditure, including skeletal muscle, liver, white adipose tissue (WAT), and brown adipose tissue (BAT). Recent evidence from pre-clinical studies with orexin knockout mice demonstrates a crucial role for the orexin system in the functionality of brown adipose tissue (BAT), probably through multiple pathways. Since BAT is a highly metabolically active organ that combusts fatty acids and glucose toward heat, thereby contributing to energy metabolism, this raises the question of whether BAT plays a role in the development of obesity and related metabolic diseases in narcolepsy type 1. BAT is densely innervated by the sympathetic nervous system that activates BAT, for instance, following cold exposure. The sympathetic outflow toward BAT is mainly mediated by the dorsomedial, ventromedial, arcuate, and paraventricular nuclei in the hypothalamus. This review focuses on the current knowledge on the role of the orexin system in the control of energy balance, with specific focus on BAT metabolism and adiposity in both preclinical and clinical studies.

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Hypothalamic dopamine signalling regulates brown fat thermogenesis

Cited by 57 publications

References 99 publications

Dopamine receptor D1- and D2-agonists do not spark brown adipose tissue thermogenesis in mice

Dopamine receptor D1- and D2-agonists do not spark brown adipose tissue thermogenesis in mice

Vulnerable and Resilient Phenotypes in a Mouse Model of Anorexia Nervosa

Role of Brown Adipose Tissue in Adiposity Associated With Narcolepsy Type 1

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