Hypothalamic feeding circuits have been identified as having innate synaptic plasticity, mediating adaption to the changing metabolic milieu by controlling responses to feeding and obesity. However, less is known about the regulatory principles underlying the dynamic changes in agouti-related protein (AgRP) perikarya, a region crucial for gating of neural excitation and, hence, feeding. Here we show that AgRP neurons activated by food deprivation, ghrelin administration, or chemogenetics decreased their own inhibitory tone while triggering mitochondrial adaptations in neighboring astrocytes. We found that it was the inhibitory neurotransmitter GABA released by AgRP neurons that evoked this astrocytic response; this in turn resulted in increased glial ensheetment of AgRP perikarya by glial processes and increased excitability of AgRP neurons. We also identified astrocyte-derived prostaglandin E₂, which directly activated — via EP2 receptors — AgRP neurons. Taken together, these observations unmasked a feed-forward, self-exciting loop in AgRP neuronal control mediated by astrocytes, a mechanism directly relevant for hunger, feeding, and overfeeding.

In the presence of high abundance of exogenous fatty acids, cells either store fatty acids in lipid droplets or oxidize them in mitochondria. In this study, we aimed to explore a novel and direct role of mitochondrial fission in lipid homeostasis in HeLa cells. We observed the association between mitochondrial morphology and lipid droplet accumulation in response to high exogenous fatty acids. We inhibited mitochondrial fission by silencing dynamin-related protein 1(DRP1) and observed the shift in fatty acid storage-usage balance. Inhibition of mitochondrial fission resulted in an increase in fatty acid content of lipid droplets and a decrease in mitochondrial fatty acid oxidation. Next, we overexpressed carnitine palmitoyltransferase-1 (CPT1), a key mitochondrial protein in fatty acid oxidation, to further examine the relationship between mitochondrial fatty acid usage and mitochondrial morphology. Mitochondrial fission plays a role in distributing exogenous fatty acids. CPT1A controlled the respiratory rate of mitochondrial fatty acid oxidation but did not cause a shift in the distribution of fatty acids between mitochondria and lipid droplets. Our data reveals a novel function for mitochondrial fission in balancing exogenous fatty acids between usage and storage, assigning a role for mitochondrial dynamics in control of intracellular fuel utilization and partitioning.

Background: In response to the COVID-19 pandemic and the associated rise in anti-Asian hate crimes, we developed the Compassionate Home, Action Together program, (CHATogether) to support the mental health of the Asian American and Pacific Islander (AAPI) community.CHATogetheris a culturally informed and virtually delivered support program that harnesses the talents of AAPI teens, young adults, parents, and mental health professionals who share a commitment to serve their local communities.Methods: Our objective was to identify the active components, optimal utilization, potential benefits, and pertinent limitations of theCHATogetherprogram during the 3 years since its inception in 2019. By that time, the program had developed six distinct component arms: interactive theater, mental health education, research, peer support and community outreach, collaboration, and AAPI mentorship. To work towards this objective, we conducted a qualitative study using thematic analysis and an inductive approach based on grounded theory (GT), in which we analyzed anonymized transcripts of four focus groups, comprised of 20 program participants (11 females; 9 males).Results: We developed a model of two overarching domains, each with three underlying themes: I. Individual stressors: (1) Family conflict; (2) Cultural identity; and (3) Pandemic impact; and II. Collective stressors: (1) Stigma related to mental health and illness; (2) Pandemic uncertainty; and (3) Xenophobia and societal polarization. Strengths of theCHATogetherprogram include its role as a conduit toward AAPI connectedness and pride as well as purpose in building community. Through support and mentorship, the program cultivates a unique platform that promotes healing and resiliency in response to pandemic stressors and beyond.Conclusions: CHATogethercreates a safe space for the AAPI community. Through its methods of storytelling and encouraging creativity,CHATogetherfacilitates the discussion of challenging topics specific to the AAPI community. Given the national mental health crisis that is further being exacerbated by the COVID-19 pandemic, a digital prevention program such asCHATogetherholds promise towards providing access to mental health resources and supporting early help-seeking behaviors for individuals in the AAPI community.

The bioenergetic function of mitochondrial fission is associated with uncoupled respiration or elimination of damaged mitochondria to maintain a healthy mitochondrial population. In the presence of a high abundance of exogenous fatty acids, cells can either store fatty acids in lipid droplets or oxidize them in mitochondria. Even though carnitine palmitoyltransferase-1 (CPT1) controls the respiratory capacity of mitochondria in fatty acid oxidation, we observed that it did not dictate the balance of storage and usage of lipids in HeLa cells. On the other hand, inhibition of mitochondrial fission by silencing dynamic-related protein 1 (DRP1) resulted in an increase in fatty acid content of lipid droplets and a decrease in fatty acid oxidation. Mitochondrial fission was not only reflective of the amount of exogenous fatty acid being processed by mitochondria, but also found to be actively involved in the distribution of fatty acids between mitochondria and lipid droplets. Our data reveals a novel function for mitochondrial fission in balancing exogenous fatty acids between usage and storage, assigning a role for mitochondrial dynamics in control of intracellular fuel utilization and partitioning.