Posted on Jun 29, 2019, 7 p.m.
According to a study published in Science, obesity may hinder activity of neurons in the lateral hypothalamic area associated with controlling eating behaviors to basically take the brakes off food intake which further fuels pathological eating and obesity.
Garret D. Stuber, PhD and colleagues from the University of North Carolina report, “findings demonstrate how diet disrupts the function of an endogenous feeding suppression system to promote overeating and obesity.”
Over 500 million adults are affected by obesity which is associated with a range of health issues; despite the increasing global prevalence how obesity impacts neurological mechanisms that may contribute to eating behaviors that promote obesity is not fully understood, but previous research suggests that the lateral hypothalamic area may play a role in eating behavior.
A series of tests were carried out in mouse models of obesity to investigate changes in the activity of different subsets of neurons in the LHA; high throughput single cell RNA sequencing was conducted to assess differential gene expression in LHA neurons in lean mice fed a normal diet, and in obese mice fed a high fat diet which revealed a subset of glutamatergic neurons expressing vesicular glutamate transporter type-2 as exhibiting changes in the greatest proportion of genes, including those associated with neuronal activity.
“Consistently, LHAVglut2 neurons also contained the most significant gene-level genetic association with human body mass index (BMI), suggesting that similar alterations within LHAVglut2 neurons may contribute to human obesity.”
In another series of tests involving two photon calcium imaging of single neurons, in control mice individual LHAVglut2 neurons responded to the animals licking sucrose, this neuronal excitation acted to dampen further feeding, and the level of response depended on the animals’ motivation to feed.
“After prefeeding, when motivation for food was low, LHAVglut2 responses of the same neurons were greater than those after a 24-hour fast. The neural responses during sucrose consumption could thus be used to decode the motivational state of each mouse. The difference in LHAVglut2neuronal response to sucrose consumption was independent to differences in lick rate, suggesting that satiety modified LHAVglut2 reward encoding independently of specific motor output.”
“Here, we demonstrate that LHAVglut2 neurons are sensitive to satiety state: when motivation for food is low, they are more excitable than when motivation is high. Reasoning that an HFD might modify the dynamics of LHAVglut2 neuron activity, the team then demonstrated that LHA Vglut2 neurons from HFD mice became progressively less responsive to sucrose consumption.”
“Until now, obesity’s effects on the LHA have been unclear,” they stated. “We hypothesize that the excitatory LHAVglut2 signal represents the activation of a brake on feeding to suppress further food intake … Chronic HFD modification within LHAVglut2 cells ultimately hinders their neuronal activity, thereby weakening an endogenous attenuator of feeding to promote overeating and obesity.”
The researchers noted that it is not known whether dampening LHAVglut2 neuronal excitation induced by high fat diet feeding would revert back to responsive states if the diet was also normalized, or whether other homeostatic challenges might also influence neuronal activity. “Further understanding of the multifunctionality within this population could identify new therapeutic targets for eating disorders and obesity.”
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