Impact of obesity and diet on brain structure and function: a gut–brain–body crosstalk

Abstract

Most societies witness an ever increasing prevalence of both obesity and dementia, a scenario related to often underestimated individual and public health burden. Overnutrition and weight gain have been linked with abnormal functionality of homoeostasis brain networks and changes in higher cognitive functions such as reward evaluation, executive functions and learning and memory. In parallel, evidence has accumulated that modifiable factors such as obesity and diet impact the gut–brain axis and modulate brain health and cognition through various pathways. Using neuroimaging data from epidemiological studies and randomised clinical trials, we aim to shed light on the underlying mechanisms and to determine both determinants and consequences of obesity and diet at the level of human brain structure and function. We analysed multimodal 3T MRI of about 2600 randomly selected adults (47 % female, 18–80 years of age, BMI 18–47 kg/m2) of the LIFE-Adult study, a deeply phenotyped population-based cohort. In addition, brain MRI data of controlled intervention studies on weight loss and healthy diets acquired in lean, overweight and obese participants may help to understand the role of the gut–brain axis in food craving and cognitive ageing. We find that higher BMI and visceral fat accumulation correlate with accelerated brain age, microstructure of the hypothalamus, lower thickness and connectivity in default mode- and reward-related areas, as well as with subtle grey matter atrophy and white matter lesion load in non-demented individuals. Mediation analyses indicated that higher visceral fat affects brain tissue through systemic low-grade inflammation, and that obesity-related regional changes translate into cognitive disadvantages. Considering longitudinal studies, some, but not all data indicate beneficial effects of weight loss and healthy diets such as plant-based nutrients and dietary patterns on brain ageing and cognition. Confounding effects of concurrent changes in other lifestyle factors or false positives might help to explain these findings. Therefore a more holistic intervention approach, along with open science tools such as data and code sharing, in-depth pre-registration and pooling of data could help to overcome these limitations. In addition, as higher BMI relates to increased head micro-movements during MRI, and as head motion in turn systematically induces image artefacts, future studies need to rigorously control for head motion during MRI to enable valid neuroimaging results. In sum, our results support the view that overweight and obesity are intertwined with markers of brain health in the general population, and that weight loss and plant-based diets may help to promote brain plasticity. Meta-analyses and longitudinal cohort studies are underway to further differentiate causation from correlation in obesity- and nutrition-brain research.

The Influence of Obesity on Cognitive Functioning Among Healthcare Professionals: A Comprehensive Analysis

“…According to studies by Medawar et al, 2022, people who have a higher BMI and more visceral fat also tend to have more subtle grey matter atrophy and white matter lesions, a different hypothalamic microstructure, and decreased thickness, memory, and connectivity in reward and default mode network regions. Analysis of mediation showed that localized anomalies linked to obesity result in cognitive deficits and that increasing visceral fat adversely affects brain tissue via systemic low-grade inflammation [ 19 ]. Similarly, memory and neuroanatomical assessments were shown to be generally declining in our study.…”

Obesity Becomes a Global Problem

“…External factors also have a big influence because from an early age the environment judges fat people as lazy, stupid and slow. (Medawar & Witte, 2022)…”

Neurobiology of eating behavior, nutrition, and health

“…Diet and obesity can blunt higher cognitive (hippocampal and PFC) functioning, which negatively influences future decision making in support of health behaviors. Investigations in mouse models have not revealed conclusive mechanisms, whereby obesity and undernutrition affect neuronal circuitry [94,95]. Although current technologies have revealed the architecture of neuronal connections and synapses in mice, they cannot detect changes in the strength of existing brain connections at synaptic and axonal development levels.…”