Publications by authors named "John T Garretson"

Aberrant neuronal DNA methylation patterns have been implicated in the promotion of obesity development; however, the role of neuronal DNA methyltransferases (Dnmts), enzymes that catalyze DNA methylation, in energy balance remains poorly understood. We investigated whether neuronal Dnmt1 regulates normal energy homeostasis and obesity development using a neuronal Dnmt1 knockout (ND1KO) mouse model, Dnmt1fl/fl Synapsin1Cre, which specifically deletes Dnmt1 in neurons. Neuronal Dnmt1 deficiency reduced adiposity in chow-fed mice and attenuated obesity in high-fat diet (HFD)-fed male mice.

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  • The study investigates how metabolic challenges like cold exposure activate sensory nerves in white adipose tissue (WAT), which leads to lipolysis and increases free fatty acids for energy in brown adipose tissue (BAT).* -
  • Researchers tested this by evaluating the effects of sympathetic nervous system stimulants on WAT afferent nerve activity in Siberian hamsters and found that lipolysis triggers these nerves.* -
  • Results show that WAT lipolysis activates a neural pathway that leads to increased BAT thermogenesis, indicating a direct connection between these two types of adipose tissue during metabolic challenges.*
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  • - PPARγ is targeted for type II diabetes treatment but can lead to increased food intake and body fat, so this study investigates its role in feeding behaviors using Siberian hamsters and C57BL/6 mice.
  • - The research tested how the PPARγ agonist rosiglitazone (ROSI) and the antagonist GW9662 affect feeding behaviors, as well as the impacts of food deprivation on specific mRNA expressions, particularly agouti-related protein (AgRP) and neuropeptide Y (NPY).
  • - Results showed that ROSI increases food hoarding and intake while also promoting AgRP and NPY expression, suggesting PPARγ activation plays a critical role in controlling these ingestive behaviors,
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Brown adipose tissue (BAT) is an important source of thermogenesis which is nearly exclusively dependent on its sympathetic nervous system (SNS) innervation. We previously demonstrated the SNS outflow from brain to BAT using the retrograde SNS-specific transneuronal viral tract tracer, pseudorabies virus (PRV152) and demonstrated the sensory system (SS) inflow from BAT to brain using the anterograde SS-specific transneuronal viral tract tracer, H129 strain of herpes simplex virus-1. Several brain areas were part of both the SNS outflow to, and receive SS inflow from, interscapular BAT (IBAT) in these separate studies suggesting SNS-SS feedback loops.

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  • Food hoarding in both animals and humans is an evolutionary trait that helps them survive during times of limited resources.
  • Humans, unlike what some might think, do not overeat after fasting; instead, they increase their food hoarding, a behavior similar to that of hamsters.
  • Research with male Siberian hamsters showed that their food hoarding behavior was affected by the size of their food stash, indicating that their hoarding behavior is more of a regulated response rather than just a reaction to hunger.
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  • Ghrelin is a hormone from the stomach that signals hunger, with its activity relying on a modification called octanoylation, which is facilitated by an enzyme called GOAT.
  • In studies on Siberian hamsters, inhibiting GOAT with a compound called GO-CoA-Tat resulted in reduced food-seeking and intake behaviors after food deprivation, suggesting that octanoylated ghrelin is key to stimulating eating.
  • This research highlights the complex mechanisms of hunger regulation and suggests that targeting ghrelin could be important for developing treatments for human eating behaviors and weight management.
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