Early exposure to high-fat diet impairs central and peripheral metabolic function: Impacts on cognition and mitochondrial function

Vilela, W. R.; Bellozi, P. M. Q.; Picolo, V. L.; Cavadas, B. N.; Marques, K. V. S.; Pereira, L. T. G.; Amato, A. A.; Magalhaes, K. G.; Mortari, M. R.; Goulart, J. T.; de Bem, A. F.

doi:10.1101/2022.06.22.496258

bioRxiv · 10.1101/2022.06.22.496258

Early exposure to high-fat diet impairs central and peripheral metabolic function: Impacts on cognition and mitochondrial function

Vilela, W. R.·Bellozi, P. M. Q.·Picolo, V. L.·Cavadas, B. N.·Marques, K. V. S.·Pereira, L. T. G.·Amato, A. A.·Magalhaes, K. G.·Mortari, M. R.·Goulart, J. T.·de Bem, A. F.

View original source ↗Export metadata ↓

Abstract

The impact of overnutrition early in life is not restricted to the onset of cardiovascular and metabolic diseases, but also affects critical brain functions related to cognition. This study aimed to evaluate the relationship between peripheral metabolic and bioenergetic changes induced by high-fat diet (HFD) and their impact on hippocampal cognitive functions in juvenile mice. To this purpose, three-week-old male C57BL/6 mice received a HFD or control diet for seven weeks, associated with two low doses of streptozotocin (STZ) or vehicle, to accelerate the metabolic dysfunction. HFD induced metabolic changes in mice, particularly related to glucose metabolism, in spite of the absence of obesity and changes in lipid profile. HFD exposure starting from weaning impaired recognition and spatial memories in mice, without inducing a depressive-like behavior. Increased immunoreactivity for GFAP and a trend towards a decrease in NeuN staining were verified in the hippocampus of HFD-fed mice. HFD caused a bioenergetic impairment in the hippocampus, characterized by a decrease in both O2 consumption related to ATP production and in the maximum respiratory capacity. The thermogenic capacity of brown adipose tissue was impaired by HFD, here verified through the absence of a decrease in O2 consumption after UCP-1 inhibition and increase in the reserve respiratory capacity. Impaired mitochondria function was also observed in the liver of HFD mice, while no changes were verified in O2 consumption in the heart of juvenile mice. These results indicate that the introduction of a HFD early in life has a detrimental impact on bioenergetic and mitochondrial function of tissues with metabolic and thermogenic activities, which is likely related to hippocampal metabolic changes and cognitive impairment. HighlightsO_LIHFD introduced early in life impacts mitochondrial function C_LIO_LIDietary shift early in life leads hippocampal dysfunction C_LIO_LIEarly life HFD exposure disrupts BAT thermogenic acitivity C_LIO_LIHFD-induced hippocampal and BAT mitochondrial dysfunction impacts cognition C_LI

Source connections

Published article ↗

Explore related subjects

neuroscience Preprint

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Vilela, W. R., Bellozi, P. M. Q., Picolo, V. L., Cavadas, B. N., Marques, K. V. S., Pereira, L. T. G., Amato, A. A., Magalhaes, K. G., Mortari, M. R., Goulart, J. T., de Bem, A. F.. 2022-06-26. Early exposure to high-fat diet impairs central and peripheral metabolic function: Impacts on cognition and mitochondrial function. https://doi.org/10.1101/2022.06.22.496258

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Novel Tau Interaction Partners as Potential Biomarkers and Therapeutic Targets in Neurodegenerative Diseases

Alzheimers disease is a progressive neurodegenerative disorder leading to cognitive decline and ultimately death. One of the main hallmarks of this disease is the accumulation of pathological tau protein into neurofibrillary tangles. To better understand these pathological mechanisms, it is essential to characterize the tau protein interactome in health and disease. In this study, we performed a yeast two-hybrid screening using a human brain cDNA library, from which we identified 15 novel tau-interacting proteins that bind to full-length human tau, or its fragments: the N-terminus, microtubule-binding domain, or C-terminus. We subsequently validated these novel interactions using in vitro co-immunoprecipitation and colocalization assays with both physiological and pathological tau isoforms. Furthermore, their interactions with the human tau protein were analyzed using surface plasmon resonance. Finally, an in silico interactome analysis of these newly discovered tau-binding partners revealed several additional interactors that can link them to downstream processes critical to neurodegenerative pathways Our findings offer fresh insights into tau biology and highlight novel targets for therapeutic intervention and biomarker development.

neuroscience↗

bioRxiv2026

Early visual cortex is not functionally necessary for temporal attention: A TMS study

Temporal attention enhances the selective processing of information at a specific point in time and improves perception. Previous neuroimaging studies investigating its neural mechanisms have either conflated temporal attention with temporal expectation or provided correlational evidence. Thus, whether early visual cortex is functionally necessary for temporal attention remains unknown. Here, we combined psychophysics with transcranial magnetic stimulation (TMS) to examine whether V1/V2 are functionally necessary and play a causal role in temporal attention. Observers performed an orientation-discrimination task in which two consecutive stimuli, T1 and T2, were presented in the periphery, preceded by a precue providing either valid or neutral temporal information. Double-pulse TMS was delivered under four conditions: at T1 (T1-TMS), at T2 (T2-TMS), at both T1 and T2 (both-TMS), or not at all (none-TMS), to assess its effects on temporal attention and the efficacy of the stimulation was verified by pupil size analysis. Behavioral results revealed robust temporal attention benefits on d', reaction time, and the Balanced Integration Score (BIS) across all four TMS conditions, indicating that the benefits of temporal attention were unaffected by occipital TMS. Furthermore, pupil dilation was largest in the both-TMS condition, followed by the T1-TMS and T2-TMS conditions, and smallest in the none-TMS condition, providing physiological verification of the stimulation protocol. Together, these findings reveal the first causal evidence that the early visual cortex is not functionally necessary for endogenous temporal attention.

neuroscience↗

bioRxiv2026

Disentanglement of persistent and dynamic neural substrates of working memory

Competing theories of working memory have alternatively emphasized the importance of persistent and dynamic substrates of this cognitive function. Here, we directly tested these theories by computationally isolating the contributions of persistent and dynamic activity to working memory. We analyzed neuronal population activity recordings in macaques doing match/non-match working memory tasks. We first extracted signatures of persistent and dynamic activity through cue-specific temporal means, temporal principal components, and correlations of activity patterns across task epochs. We then generated synthetic data constrained by these signatures, and decoded cue stimuli from these data, separately from persistent and non-persistent neurons. We found that high decoding performance arose from a nuanced interplay of persistent and dynamic activity. Specifically, we could decode stimuli at empirical or above-chance levels across all tasks only from persistent neurons, but only after constraining correlations of activity patterns across epochs. In this way, we showed distinct roles for persistent and dynamic neuronal activity that help to unify two competing theories of working memory. More broadly, we also advanced computational controlled experiments as a principled framework for adjudicating between competing models of neuronal population activity.

neuroscience↗