Protein-coding mutation in Adcy3 increases adiposity and alters emotional behaviors sex-dependently in rats.

Objective: Adenylate cyclase 3 (Adcy3) has been linked to both obesity and major depressive disorder. We identified a protein-coding variant in the transmembrane (TM) helix of Adcy3 in rats; similar obesity variants have been identified in humans. This study investigates the role of a TM variant in adiposity and behavior.

Protein-coding mutation in increases adiposity and alters emotional behaviors sex-dependently in rats.

Objective: has been linked to both obesity and major depressive disorder (MDD). Our lab identified a protein-coding variant in the 2 transmembrane (TM) helix of in rats, and similar obesity variants have been identified in humans. The current study investigates the role of a TM variant in adiposity and behavior.

Chronic stress from adolescence to adulthood increases adiposity and anxiety in rats with decreased expression of .

We previously identified , , as a novel adiposity gene, but subsequently found that its impact on adiposity may depend on environmental stress. To more thoroughly understand the connection between , adiposity, and stress, we exposed wild-type (WT) and knock-out (KO) rats to chronic stress then measured adiposity and behavioral outcomes. We found that KO rats displayed lower basal stress than WT rats under control conditions and exhibited metabolic and behavioral responses to chronic stress exposure.

Changes in environmental stress over COVID-19 pandemic likely contributed to failure to replicate adiposity phenotype associated with .

We previously identified keratinocyte-associated protein 3, , as an obesity-related gene in female rats where a whole body knockout (KO) led to increased adiposity compared to wild-type (WT) controls when fed a high-fat diet (HFD). We sought to replicate this work to better understand the function of but were unable to reproduce the adiposity phenotype. In the current work, WT female rats ate more compared to WT in the prior study, with corresponding increases in body weight and fat mass, while there were no changes in these measures in KO females between the studies.

Changes in Environmental Stress over COVID-19 Pandemic Likely Contributed to Failure to Replicate Adiposity Phenotype Associated with Krtcap3.

We previously identified Keratinocyte-associated protein 3, Krtcap3, as an obesity-related gene in female rats where a whole-body Krtcap3 knock-out (KO) led to increased adiposity compared to wild-type (WT) controls when fed a high-fat diet (HFD). We sought to replicate this work to better understand the function of Krtcap3 but were unable to reproduce the adiposity phenotype. In the current work, WT female rats ate more compared to WT in the prior study, with corresponding increases in body weight and fat mass, while there were no changes in these measures in KO females between the studies.

Genetic Disruption of System xc-Mediated Glutamate Release from Astrocytes Increases Negative-Outcome Behaviors While Preserving Basic Brain Function in Rat.

The importance of neuronal glutamate to synaptic transmission throughout the brain illustrates the immense therapeutic potential and safety risks of targeting this system. Astrocytes also release glutamate, the clinical relevance of which is unknown as the range of brain functions reliant on signaling from these cells hasn't been fully established. Here, we investigated system xc- (Sxc), which is a glutamate release mechanism with an rodent expression pattern that is restricted to astrocytes.

Genetic Mapping of Multiple Traits Identifies Novel Genes for Adiposity, Lipids, and Insulin Secretory Capacity in Outbred Rats.

Despite the successes of human genome-wide association studies, the causal genes underlying most metabolic traits remain unclear. We used outbred heterogeneous stock (HS) rats, coupled with expression data and mediation analysis, to identify quantitative trait loci (QTLs) and candidate gene mediators for adiposity, glucose tolerance, serum lipids, and other metabolic traits. Physiological traits were measured in 1,519 male HS rats, with liver and adipose transcriptomes measured in >410 rats.

plays a role in body weight and adiposity with differential effects in males and females.

Despite the obesity crisis in the United States, the underlying genetics are poorly understood. Our lab previously identified as a candidate gene for adiposity through a genome-wide association study in outbred rats, where increased liver expression of correlated with decreased fat mass. Here we seek to confirm that expression affects adiposity traits.

Maternal diet during gestation and lactation modifies the severity of salt-induced hypertension and renal injury in Dahl salt-sensitive rats.

Environmental exposure of parents or early in life may affect disease development in adults. We found that hypertension and renal injury induced by a high-salt diet were substantially attenuated in Dahl SS/JrHsdMcwiCrl (SS/Crl) rats that had been maintained for many generations on the grain-based 5L2F diet compared with SS/JrHsdMcwi rats (SS/Mcw) maintained on the casein-based AIN-76A diet (mean arterial pressure, 116±9 versus 154±25 mm Hg; urinary albumin excretion, 23±12 versus 170±80 mg/d). RNAseq analysis of the renal outer medulla identified 129 and 82 genes responding to a high-salt diet uniquely in SS/Mcw and SS/Crl rats, respectively, along with minor genetic differences between the SS substrains.