Early life overnutrition impairs plasticity of non-neuronal brainstem cells and drives obesity in offspring across development in rats

Abstract

Background The prevalence of adolescent obesity has increased dramatically, becoming a serious public health concern. While previous evidence suggests that in utero-and early postnatal overnutrition increases adult-onset obesity risk, the neurobiological mechanisms underlying this outcome are not well understood. Non-neuronal cells play an underestimated role in the physiological responses to metabolic/nutrient signals. Hypothalamic glial-mediated inflammation is now considered a contributing factor in the development and perpetuation of obesity; however, attention on the role of gliosis and microglia activation in other nuclei is still needed. Methods/results Here, we demonstrate that early life consumption of high-fat/sucrose diet (HFSD) is sufficient to increase offspring body weight, hyperleptinemia and potentially maladaptive cytoarchitectural changes in the brainstem dorsal-vagalcomplex (DVC), an essential energy balance processing hub, across postnatal development. Our data demonstrate that preand postnatal consumption of HFSD result in increased body weight, hyperleptinemia and dramatically affects the nonneuronal landscape, and therefore the plasticity of the DVC in the developing offspring. Conclusions Current findings are very provocative, considering the importance of the DVC in appetite regulation, suggesting that HFSD-consumption during early life may contribute to subsequent obesity risk via DVC cytoarchitectural changes.

Obesity and its associated factors among older adults: MyHEBAT (Malaysian HEalth and Well‐Being AssessmenT) study

“… 30 , 31 , 32 Collectively, several studies have agreed that obesity is common especially in people with higher income status, which is probably due to higher income people usually consume more fatty and sweet diets, living sedentary lifestyles, and being too busy to cook healthy low‐cholesterol meal at home. 33 , 34 , 35 Moreover, the lifestyles and dietary habits of Malaysians are likely to play a role in causing obesity, especially among elderly adults. 36 , 37 Although clinical preventive services and health promotion programs were implemented to identify and control hypertension, diabetes and CVD among older adult females, especially those who had tertiary level of education, a comprehensive nation‐wide medical priorities on these risk factors are still have to be taken.…”

“…Binary logistic regression results (Table A5) showed that obesity was significantly associated with those aged between 70 and 79 years old, female, non‐Malay, with tertiary level education, monthly income ≥RM3000, has diabetes, hypertension, family history of hypertension, and a family history of CVD 30‐32 . Collectively, several studies have agreed that obesity is common especially in people with higher income status, which is probably due to higher income people usually consume more fatty and sweet diets, living sedentary lifestyles, and being too busy to cook healthy low‐cholesterol meal at home 33‐35 . Moreover, the lifestyles and dietary habits of Malaysians are likely to play a role in causing obesity, especially among elderly adults 36,37 .…”

The role of glia in the physiology and pharmacology of glucagon‐like peptide‐1: implications for obesity, diabetes, neurodegeneration and glaucoma

“…As research efforts examining GLP‐1 action on astrocytes and microglia intensify, and with respect to experiments looking at the contribution of glia to energy balance control, it is important to remember that glia are an unique and dynamic group of cells in constant states of transcriptomic and morphological flux. In the context of energy balance, study results have clearly shown that perturbations to diet and/or energy states can influence the in situ cytoarchitecture of hypothalamic and brainstem DVC astrocytes, as well as microglia morphology and activity (Fuente‐Martin et al, 2012; Garcia‐Caceres et al, 2011; J. G. Kim et al, 2014; Liberini et al, 2020; MacDonald et al, 2020; Stein et al, 2020). Interpretation of GLP‐1 action on glia is therefore affected by multiple factors that include, but are not limited to, age, diet and energy states (i.e.…”

“…Another intriguing but understudied glial population relevant to CNS ligand trafficking are tanycytes. Tanycytes are specialized, polarized ependymocytes that line the floor of the third ventricle in the median eminence and the subpostrema subnuclei that connects the area postrema (AP) to the nucleus tractus solitarius (NTS) in the caudal brainstem (Guillebaud et al, 2017; Langlet et al, 2013; Liberini et al, 2020; Prevot et al, 2013). These unique cells allow for trafficking of circulating signals relevant to food intake and energy balance control to adjacent neurons in the basal hypothalamic arcuate nucleus and the AP/NTS, respectively.…”

“…Because GLP-1Rs are expressed on infiltrating macrophages (Shiraishi et al, 2012), a challenge for the GLP-1 field will be to differentiate between macrophage-mediated and glia-mediated GLP-1 function when using these approaches. Kim et al, 2014;Liberini et al, 2020;MacDonald et al, 2020;Stein et al, 2020). Interpretation of GLP-1 action on glia is therefore affected by multiple factors that include, but are not limited to, age, diet and energy states (i.e.…”