Biology subjects

Kamitakahara, A. K.

Publications and source records attributed to Kamitakahara, A. K..

5 recordsLinked to original sources

bioRxiv2026

Tyrosine hydroxylase deletion in Ntsr1 neurons confers resistance to diet-induced weight gain: an energy-balance analysis

High-fat diet (HFD) disrupts circadian feeding rhythms and promotes diet-induced obesity (DIO), but the neural mechanisms linking diet to energy balance remain unclear. Previously, we demonstrated that dopamine production in neurotensin receptor 1 (Ntsr1)-expressing neurons was required for HFD-induced daytime overfeeding and DIO. Here, we tested whether DIO resistance in Ntsr1Cre;Thflox conditional knockout (cKO) mice was explained by altered energy expenditure. We replicated resistance to HFD-induced weight gain and assessed food intake, indirect calorimetry, activity, body temperature, fecal energy, fecal nonesterified fatty acids, and the gut microbiome. Indirect calorimetry on standard chow diet (SCD) was confounded by reduced intake and body weight loss, whereas HFD-fed cKO mice consumed food readily and resisted weight gain. Unlike our previous study, daytime feeding was not suppressed; instead, cKO mice were slightly and variably hypophagic on HFD but not SCD. DIO resistance was not accompanied by increased energy expenditure, activity, or body temperature. Rather, cKO mice showed reduced energy expenditure and activity and lower body temperature on both diets. In the replication cohort, HFD fecal output was lower in cKO mice, whereas the independent bomb-calorimetry cohort showed no genotype difference in fecal mass; fecal energy density and nonesterified fatty acid concentration were unchanged. Preliminary analysis of the microbiome was consistent with an obesity-resistant gut profile. Together, these findings indicate that the feeding phenotype is diet- and experiment-dependent and that DIO resistance is not explained by increased energy expenditure, activity, thermogenesis, or detectable changes in fecal energy or fat content.

neuroscience↗

bioRxiv2026

Early ingestive experience with a high-fat diet tunes satiation and nutrient-specific appetitive behaviors

Overconsumption of foods rich in fats, sugars, and calories is a major contributing factor to increased risk for cardiometabolic disease. Ingestive experience with these foods can begin early in children, yet there is limited understanding of the impact of early life nutrition on the development of vagal afferent neurons necessary for coordinating appetitive and satiating behaviors. To address this gap, mice reared on a chow diet (control) were compared to those reared on a high-fat diet (HFDEARLY). We demonstrate that the vagally-mediated satiation response to cholecystokinin (CCK) does not mature until adolescence in chow-reared mice. However, HFDEARLY exposure triggers a precocious maturation of this response, accompanied by transcriptomic changes in the nodose ganglion. Durable changes in appetitive behaviors were also evident in adult HFDEARLY mice, which consumed more lipid than control mice. Behavioral analyses point to alterations in orosensory processing and enhanced appetition in adult HFDEARLY mice. Furthermore, female HFDEARLY mice showed a selective increase in consumption of a calorie-dense liquid diet in adulthood, accompanied by changes in body composition, suggesting a lasting, sex-specific vulnerability to overconsumption of palatable, energy-dense foods. Together, these results establish nutrient exposure as a significant contributor to vagal circuit maturation and function.

animal behavior and cognition↗

bioRxiv2022

Ontogeny of Vagal Sensory Cell Types and Trophic Factor Sensitivity

Vagal sensory neurons located in the nodose ganglion provide a direct line of communication from the gut to the brain. Information, such as stomach stretch or the presence of ingested nutrients in the intestine, is conveyed to the caudal medulla via specialized cell types that express unique marker genes. Here, we leverage vagal cell type marker genes identified in adult mice to determine when specialized vagal subtypes arise developmentally, as well as the factors that shape their growth and target innervation. Initial sequencing and pathway analysis comparing early postnatal to adult nodose ganglia identified an enrichment of differentially expressed genes (DEGs) related to axon growth and guidance, synaptic strengthening, and DEGs downstream of brain derived neurotrophic factor (BDNF). Subsequent experiments performed to screen for trophic factor sensitivity revealed that both BDNF and glial cell derived neurotrophic factor (GDNF) robustly stimulate neurite outgrowth from early postnatal nodose ganglion explants in vitro. Anatomical examination of whole-body trophic factor expression in perinatal mice revealed that BDNF is expressed by neurons of the nodose ganglion itself, while GDNF is expressed by developing intestinal smooth muscle cells. Thus, BDNF may support vagal neurons as a locally derived trophic factor, while GDNF may act as a target derived trophic factor supporting the growth of vagal sensory processes at distal innervation sites in the gut. Consistent with this, expression of the GDNF receptor, Gfra1, was enriched in vagal afferent cell types that project to the gastrointestinal tract. The BDNF receptor, Ntrk2, was expressed by the majority vagal sensory neurons, irrespective of cell type. Lastly, spatial mapping of genetic markers in the nodose ganglion demonstrates that defined vagal cell types begin to emerge as early as embryonic day 13, even as sensory neurons continue to grow to reach gastrointestinal targets. Despite the early onset of expression for some cell type marker genes, expression patterns of many individual cell type markers appear largely immature in prenatal life and mature considerably by the end of the first postnatal week. Together, the data support a role for GDNF in stimulating vagal sensory growth to gastrointestinal targets and establish a prolonged perinatal timeline for vagal sensory cell type maturation.

neuroscience↗

bioRxiv2020

Ghrelin signaling regulates feeding behavior, metabolism, and memory through the vagus nerve

Vagal afferent neuron (VAN) signaling sends information from the gut to the brain and is fundamental in the neural control of feeding behavior and metabolism. Recent findings reveal that VAN signaling also plays a critical role in cognitive processes, including hippocampus (HPC)-dependent memory. VANs, located in nodose ganglia, express receptors for various gut-derived endocrine signals, however, the function of these receptors with regards to feeding behavior, metabolism, and memory control is poorly understood. We hypothesized that VAN-mediated processes are influenced by ghrelin, a stomach-derived orexigenic hormone, via communication to its receptor (growth hormone secretagogue receptor [GHSR]) expressed on gut-innervating VANs. To examine this hypothesis, rats received nodose ganglia injections of an adeno-associated virus (AAV) expressing short hairpin RNAs targeting GHSR (or a control AAV) for RNA interference-mediated VAN-specific GHSR knockdown. Results reveal that VAN GHSR knockdown induced various feeding and metabolic disturbances, including increased meal frequency, impaired glucose tolerance, delayed gastric emptying, and increased body weight compared to controls. Additionally, VAN-specific GHSR knockdown impaired HPC-dependent episodic contextual memory and reduced HPC brain-derived neurotrophic factor expression, but did not affect anxiety-like behavior or levels of general activity. A functional role for endogenous VAN GHSR signaling was further confirmed by results revealing that VAN signaling is required for the hyperphagic effects of ghrelin administered at dark onset, and that gut-restricted ghrelin-induced increases in VAN firing rate require intact VAN GHSR expression. Collective results reveal that VAN GHSR signaling is required for both normal feeding and metabolic function as well as HPC-dependent memory.

neuroscience↗

bioRxiv2020

MET Receptor Tyrosine Kinase Regulates Vagal Laryngeal Motor Neuron Development and Lifespan Ultrasonic Vocal Communication

The vagal motor nucleus ambiguus (nAmb) innervates the intrinsic muscles of the larynx, providing direct motor control over vocal production in humans and rodents. Here, we demonstrate that early developmental signaling through the MET receptor tyrosine kinase (MET) is required for proper formation of the nAmb. Embryonic deletion of Met in the developing brainstem resulted in a loss of one-third of motor neurons in the nAmb. While the remaining neurons were able to establish connections with target muscles in the larynx, advanced signal processing analyses revealed severe deficits in ultrasonic vocalization in early postnatal life. Abnormal vocalization patterns persisted into adulthood in the majority of mice tested. Interestingly, 28% of adult mice recovered the ability to vocalize demonstrating heterogeneity in circuit restitution. Together, the data establish MET as a factor necessary for development of a specific subset of neurons in the nAmb required for normal ultrasonic vocalization.

neuroscience↗