Protein appetite drives macronutrient-related differences in ventral tegmental area neural activity

Abstract

Amino acids are essential for almost all biological processes and many cannot be synthesized de novo. Thus, it is crucial that all animals, including humans, acquire an adequate amount of protein in their diet. Here, we show that rats maintained on a proteinrestricted diet develop a strong preference for protein, relative to carbohydrate. In addition, this preference was associated with increased neural activation in ventral tegmental area while rats were consuming protein. These changes were relatively persistent as when protein levels were restored by switching back to regular chow, behavioral preference and elevated neural activity to protein did not completely disappear. This study provides the first indication that activity in mesolimbic circuitry is involved in generating an appetite for protein in times of need.The artificial sweetener, saccharin, was used to familiarize rats with the retractable sippers in the behavioral chambers. Following five saccharin sessions, rats experienced four daily conditioning sessions in which they were given access to one bottle containing either distinctly-flavored casein (protein) or maltodextrin (carbohydrate) solutions, alternated from day to day ( Figure S2). For both solutions, rats licked more on the second session in which it

Investigating the Effect of Physiological Need States on Palatability and Motivation Using Microstructural Analysis of Licking

“…In these 'forced choice' trials, no difference in cluster number or cluster size was seen, similar to the pattern of results during conditioning in our previous study when only one bottle was available ( Figure 3B, left). These results demonstrate that, in absence of choice and a comparison between the two nutrientcontaining solutions, rats do not differ in their evaluation of each solution, which explains the similar amount of licking (Chiacchierini, et al, 2019;Murphy, et al, 2018).…”

The physiological control of eating: signals, neurons, and networks

“…For example, food restriction increases the magnitude of dopamine evoked by food consumption (142,143). A recent study has also shown that VTA dopamine neuronal activity was higher in protein-deficient rats compared to controls when they consumed a preferred protein food rather than carbohydrate (144). Work from both rodents and human neuroimaging studies is consistent in identifying the dorsal striatum as a key region receiving post-oral nutrient sensing (145)(146)(147)(148).…”

Dynamic effects of dietary protein restriction on body weights, food consumption, and protein preference in C57BL/6J and Fgf21‐KO mice

“…The use of SCEDs to evaluate the impact of these manipulations can decrease both labor and technical costs due to the use of fewer animals (in addition to the benefits associated with identifying processes that operate at the level of individual organisms). For example, a fiber photometry study measuring calcium influx in response to protein restriction, which requires intracranial injection of viral vectors and surgical insertion of photosensitive fibers for detecting calcium flux, could utilize the same animals under conditions differing in diets of varying protein content rather than utilizing different groups of mice maintained on different diets varying in protein content (e.g., Chiacchierini et al, 2021). Another interesting avenue to leverage available technologies would be to use mice in which the Fgf 21 gene is placed under control of an exogenous compound using inducible gene expression technology (for a review see Das et al, 2016) such that FGF21 production can be turned on and off during periods of protein restriction in the same animal to determine, in a reversible manner, how FGF21 production governs responses to protein restriction.…”