Feeding circuit development and early-life influences on future feeding behaviour

Abstract

A wide range of maternal exposures - undernutrition, obesity, diabetes, stress and infection - are associated with an increased risk of metabolic disease in offspring. Developmental influences can cause persistent structural changes in hypothalamic circuits regulating food intake in the service of energy balance. The physiological relevance of these alterations has been called into question because maternal impacts on daily caloric intake do not persist to adulthood. Recent behavioural and epidemiological studies in humans provide evidence that the relative contribution of appetitive traits related to satiety, reward and the emotional aspects of food intake regulation changes across the lifespan. This Opinion article outlines a neurodevelopmental framework to explore the possibility that crosstalk between developing circuits regulating different modalities of food intake shapes future behavioural responses to environmental challenges.

Mapping heritability of obesity by brain cell types

“…These data establish the ability of this approach to validate previous evidence 8 that BMI variants tend to 6 colocalize with genes specifically expressed in neurons, while also demonstrating that CELLECT is able to prioritize relevant cell types across a number of complex traits.…”

“…Our results should be interpreted in the light of the underlying data used to prioritize the cell types. First, the scRNA-seq data analyzed in the paper were derived from late postnatal (Mouse Nervous System dataset) and adult mice and hence did not cover developmental states and cell types of potential importance to obesity 6 . Second, the datasets used in this work should not be regarded as complete atlases because they are likely to miss relevant cell types (from for example the paraventricular hypothalamus, nodose ganglia and adipocytes) and cell states.…”

“…Yet growing evidence suggests that susceptibility to obesity is distributed across numerous brain areas that receive signals emanating from internal sources (e.g., viscerosensory input from the gastrointestinal tract) or external stimuli (e.g., the sight or smell of food) that act in concert to regulate feeding behavior and energy stores [5][6][7] . However, despite an increasing number of genes, cell types and neuronal circuits being implicated in murine energy homeostasis, the identity of brain cell types that drive susceptibility to human obesity remains largely unknown and a systematic assessment of cell types' relevance in obesity is currently lacking.…”

Programming of central and peripheral insulin resistance by low birthweight and postnatal catch-up growth in male mice

“…Although a genetic basis for obesity susceptibility is undisputed, only a small proportion of the BMI variation within the population can be explained by known genetic variants, suggesting there is an interaction between genetic factors and the environment [ 1 ]. Evidence from clinical and experimental studies shows that the risk of developing many non-communicable diseases can be influenced by the early-life environment [ 2 , 3 ]. Numerous studies have shown that low birthweight is associated with increased risk of developing impaired glucose tolerance and, subsequently, type 2 diabetes [ 4 , 5 ].…”

Mice with nucleus tractus solitarius injury induced by chronic restraint stress present impaired ability to raise blood glucose and glucagon levels when blood glucose levels plummet

“…Therefore, when the blood glucose levels rise or fall, NTS is the first to sense the change and then it notifies other brain regions to initiate regulation. NTS is also one of the earliest well-developed structures in the circuits of feeding and nutrition regulation [31], and this also reflects the basis and importance of NTS in metabolic regulation. [10,36].…”