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Loss of habenular Prkar2a reduces hedonic eating and increases exercise motivation.

ABSTRACT: The habenula (Hb) is a bilateral, evolutionarily conserved epithalamic structure connecting forebrain and midbrain structures that has gained attention for its roles in depression, addiction, rewards processing, and motivation. Of its 2 major subdivisions, the medial Hb (MHb) and lateral Hb (LHb), MHb circuitry and function are poorly understood relative to those of the LHb. Prkar2a codes for cAMP-dependent protein kinase (PKA) regulatory subunit II? (RII?), a component of the PKA holoenzyme at the center of one of the major cell-signaling pathways conserved across systems and species. Type 2 regulatory subunits (RII?, RII?) determine the subcellular localization of PKA, and unlike other PKA subunits, Prkar2a has minimal brain expression except in the MHb. We previously showed that RII?-knockout (RII?-KO) mice resist diet-induced obesity. In the present study, we report that RII?-KO mice have decreased consumption of palatable, "rewarding" foods and increased motivation for voluntary exercise. Prkar2a deficiency led to decreased habenular PKA enzymatic activity and impaired dendritic localization of PKA catalytic subunits in MHb neurons. Reexpression of Prkar2a in the Hb rescued this phenotype, confirming differential roles for Prkar2a in regulating the drives for palatable foods and voluntary exercise. Our findings show that in the MHb decreased PKA signaling and dendritic PKA activity decrease motivation for palatable foods, while enhancing the motivation for exercise, a desirable combination of behaviors.

SUBMITTER: London E

PROVIDER: S-EPMC7714411 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Loss of habenular Prkar2a reduces hedonic eating and increases exercise motivation.

London Edra E Wester Jason C JC Bloyd Michelle M Bettencourt Shelby S McBain Chris J CJ Stratakis Constantine A CA

JCI insight 20201203 23

The habenula (Hb) is a bilateral, evolutionarily conserved epithalamic structure connecting forebrain and midbrain structures that has gained attention for its roles in depression, addiction, rewards processing, and motivation. Of its 2 major subdivisions, the medial Hb (MHb) and lateral Hb (LHb), MHb circuitry and function are poorly understood relative to those of the LHb. Prkar2a codes for cAMP-dependent protein kinase (PKA) regulatory subunit IIα (RIIα), a component of the PKA holoenzyme at ...[more]

PMID: 33141766

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Project description:Objective. Probiotics have been reported to support healthy digestive and immune function, aid in protein absorption, and decrease inflammation. Further, a trend to increase vertical jump power has been observed following co-administration of protein and probiotics in resistance-trained subjects. However, to date the potential beneficial effect of probiotics on recovery from high intensity resistance exercise have yet to be explored. Therefore, this study examined the effect of co-administration of protein and probiotics on muscle damage, recovery and performance following a damaging exercise bout. Design. Twenty nine (n = 29) recreationally-trained males (mean ± SD; 21.5 ± 2.8 years; 89.7 ± 28.2 kg; 177.4 ± 8.0 cm) were assigned to consume either 20 g of casein (PRO) or 20 g of casein plus probiotic (1 billion CFU Bacillus coagulans GBI-30, 6086, PROBC) in a crossover, diet-controlled design. After two weeks of supplementation, perceptional measures, athletic performance, and muscle damage were analyzed following a damaging exercise bout. Results. The damaging exercise bout significantly increased muscle soreness, and reduced perceived recovery; however, PROBC significantly increased recovery at 24 and 72 h, and decreased soreness at 72 h post exercise in comparison to PRO. Perceptual measures were confirmed by increases in CK (PRO: +266.8%, p = 0.0002; PROBC: +137.7%, p = 0.01), with PROBC showing a trend towards reduced muscle damage (p = 0.08). The muscle-damaging exercise resulted in significantly increased muscle swelling and Blood Urea Nitrogen levels in both conditions with no difference between groups. The strenuous exercise significantly reduced athletic performance in PRO (Wingate Peak Power; PRO: (-39.8 watts, -5.3%, p = 0.03)), whereas PROBC maintained performance (+10.1 watts, +1.7%). Conclusions. The results provide evidence that probiotic supplementation in combination with protein tended to reduce indices of muscle damage, improves recovery, and maintains physical performance subsequent to damaging exercise.

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Loss of habenular Prkar2a reduces hedonic eating and increases exercise motivation.

Publications

Loss of habenular Prkar2a reduces hedonic eating and increases exercise motivation.

Similar Datasets

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