Biology subjects

Blevins, J. E.

Publications and source records attributed to Blevins, J. E..

7 recordsLinked to original sources

bioRxiv2026

Oxytocin and Vasopressin at Birth Prevent Hypoactivity and Excess Weight Gain in Vole Offspring Delivered by Cesarean Section

Birth occurs during a sensitive period in brain development wherein hormones facilitate the dramatic shift in physiology that accomplishes the transition to extrauterine homeostasis. The surge in birth signaling hormones is abridged in cases of delivery by cesarean section (CS), which accounts for 32% of all births in the U.S. Epidemiological studies have associated birth via CS with increased risk of obesity in later life. Here, we sought to investigate this association using an experimental preclinical animal model, the prairie vole. Subjects were delivered either via vaginal delivery (VD) or CS and then cross-fostered. CS delivery led to increased body weight across development, which could be prevented with hormone rescue of oxytocin (OXT) and arginine vasopressin (AVP), delivered to neonates immediately after CS. This weight gain could not be attributed to differences in birth weight, parenting, food consumption, or thermoregulation; however, CS subjects moved slower than VD subjects, which hormone rescue reversed. Hormone rescue also reduced adiposity in adulthood among CS subjects. The dopamine system was dysregulated in the caudate/putamen of CS offspring, suggesting a neural mechanism for the decreased locomotion. Hormone rescue of CS neonates restored dopamine synthesis in the caudate/putamen and increased spontaneous locomotor activity. These findings suggest CS can lead to increased weight gain in part through a reduction of locomotion driven by long-lasting changes in striatal dopamine regulation, all of which can be prevented by treating CS neonates with a single peripheral administration of two birth-signaling hormones, OXT and AVP.

neuroscience↗

bioRxiv2025

The Chimeric Peptide (GEP44) Reduces Body Weight, Energy Intake, and Energy Expenditure in Diet-Induced Obese Rats

We recently reported that a chimeric peptide (GEP44) targeting the glucagon-like peptide-1 receptor (GLP-1R) and neuropeptide Y1- and Y2-receptors decreased body weight (BW), energy intake and core temperature in diet-induced obese (DIO) male and female mice. In the current study, we tested the hypothesis that the strong reduction of body weight in response to GEP44 is partially related to the stimulation of energy expenditure (EE). To test this, rats were maintained on a HFD for at least 4 months to elicit DIO prior to undergoing a sequential 2-day vehicle period, 2-day GEP44 (50 nmol/kg) period and a minimum 2-day washout period and detailed measures of energy homeostasis. GEP44 (50 nmol/kg) reduced EE (indirect calorimetry), respiratory exchange ratio (RER), core temperature, activity, energy intake and BW in male and female rats. As in our previous study in mice, GEP44 reduced BW in male and female HFD-fed rats by 3.8 {+/-} 0.2% and 2.3 {+/-} 0.4%, respectively. These effects appear to be mediated by increased lipid oxidation and reductions of energy intake as GEP44 reduced RER and cumulative energy intake in male and female HFD-fed rats. The strong reduction of body weight in response to GEP44 is related to a robust reduction of energy intake, but not to stimulation of EE. The paradoxical finding that GEP44 reduced EE might be secondary to a reduction of diet-induced thermogenesis or might indicate an important mechanism to limit the overall efficacy of GEP44 to prevent further weight loss.

physiology↗

bioRxiv2024

Effects of systemic oxytocin and beta-3 receptor agonist (CL 316243) treatment on body weight and adiposity in male diet-induced obese rats

Previous studies have implicated hindbrain oxytocin (OT) receptors in the control of food intake and brown adipose tissue (BAT) thermogenesis. We recently demonstrated that hindbrain [fourth ventricle (4V)] administration of oxytocin (OT) could be used as an adjunct to drugs that directly target beta-3 adrenergic receptors ({beta}3-AR) to elicit weight loss in diet-induced obese (DIO) rodents. What remains unclear is whether systemic OT can be used as an adjunct with the {beta}3-AR agonist, CL 316243, to increase BAT thermogenesis and elicit weight loss in DIO rats. We hypothesized that systemic OT and {beta}3-AR agonist (CL 316243) treatment would produce an additive effect to reduce body weight and adiposity in DIO rats by decreasing food intake and stimulating BAT thermogenesis. To test this hypothesis, we determined the effects of systemic (subcutaneous) infusions of OT (50 nmol/day) or vehicle (VEH) when combined with daily systemic (intraperitoneal) injections of CL 316243 (0.5 mg/kg) or VEH on body weight, adiposity, food intake and brown adipose tissue temperature (TIBAT). OT and CL 316243 monotherapy decreased body weight by 8.0{+/-}0.9% (P<0.05) and 8.6{+/-}0.6% (P<0.05), respectively, but OT in combination with CL 316243 produced more substantial weight loss (14.9{+/-}1.0%; P<0.05) compared to either treatment alone. These effects were associated with decreased adiposity, energy intake and elevated TIBAT during the treatment period. The findings from the current study suggest that the effects of systemic OT and CL 316243 to elicit weight loss are additive and appear to be driven primarily by OT-elicited changes in food intake and CL 316243-elicited increases in BAT thermogenesis.

neuroscience↗

bioRxiv2024

Sympathetic innervation of interscapular brown adipose tissue is not a predominant mediator of OT-elicited reductions of body weight gain and adiposity in male diet-induced obese rats

Recent studies indicate that central administration of oxytocin (OT) reduces body weight (BW) in high fat diet-induced obese (DIO) rodents by reducing energy intake and increasing energy expenditure (EE). Previous studies in our lab have shown that administration of OT into the fourth ventricle (4V; hindbrain) elicits weight loss and stimulates interscapular brown adipose tissue temperature (TIBAT) in DIO rats. We hypothesized that OT-elicited stimulation of sympathetic nervous system (SNS) activation of IBAT contributes to its ability to activate BAT and reduce BW in DIO rats. To test this, we determined the effect of disrupting SNS activation of IBAT on OT-elicited stimulation of TIBAT and reduction of BW in DIO rats. We first confirmed that bilateral surgical SNS denervation to IBAT was successful based on having achieved [≥] 60% reduction in IBAT norepinephrine (NE) content from DIO rats. NE content was selectively reduced in IBAT by 94.7 {+/-} 2.7, 96.8 {+/-} 1.8 and 85.9 {+/-} 6.1% (P<0.05) at 1, 6 and 7-weeks post-denervation, respectively, and was unchanged in liver or inguinal white adipose tissue. We then measured the impact of bilateral surgical SNS denervation to IBAT on the ability of acute 4V OT (1, 5 {micro}g) to stimulate TIBAT in DIO rats. We found that the high dose of 4V OT (5 {micro}g) stimulated TIBAT similarly between sham and denervated rats (P=NS) and that the effects of 4V OT to stimulate TIBAT did not require beta-3 adrenergic receptor signaling. We subsequently measured the effect of bilateral surgical denervation of IBAT on the effect of chronic 4V OT (16 nmol/day) or vehicle infusion to reduce BW, adiposity, and energy intake in DIO rats. Chronic 4V OT reduced BW gain by -7.2 {+/-} 9.6 g and -14.1 {+/-} 8.8 g in sham and denervated rats (P<0.05 vs vehicle treatment), respectively, and this effect was similar between groups (P=NS). These effects were associated with reductions in adiposity and energy intake (P<0.05). Collectively, these findings support the hypothesis that sympathetic innervation of IBAT is not required for central OT to increase BAT thermogenesis and reduce BW gain and adiposity in male DIO rats.

neuroscience↗

bioRxiv2024

Sympathetic innervation of interscapular brown adipose tissue is not a predominant mediator of oxytocin-elicited reductions of body weight and adiposity in male diet-induced obese mice

Previous studies indicate that CNS administration of oxytocin (OT) reduces body weight in high fat diet-induced obese (DIO) rodents by reducing food intake and increasing energy expenditure (EE). We recently demonstrated that hindbrain (fourth ventricular [4V]) administration of OT elicits weight loss and elevates interscapular brown adipose tissue temperature (TIBAT, a surrogate measure of increased EE) in DIO mice. What remains unclear is whether OT-elicited weight loss requires increased sympathetic nervous system (SNS) outflow to IBAT. We hypothesized that OT-induced stimulation of SNS outflow to IBAT contributes to its ability to activate BAT and elicit weight loss in DIO mice. To test this hypothesis, we determined the effect of disrupting SNS activation of IBAT on the ability of 4V OT administration to increase TIBAT and elicit weight loss in DIO mice. We first determined whether bilateral surgical SNS denervation to IBAT was successful as noted by [≥] 60% reduction in IBAT norepinephrine (NE) content in DIO mice. NE content was selectively reduced in IBAT at 1-, 6- and 7-weeks post-denervation by 95.9{+/-}2.0, 77.4{+/-}12.7 and 93.6{+/-}4.6% (P<0.05), respectively and was unchanged in inguinal white adipose tissue, pancreas or liver. We subsequently measured the effects of acute 4V OT (1, 5 {micro}g {approx} 0.99, 4.96 nmol) on TIBAT in DIO mice following sham or bilateral surgical SNS denervation to IBAT. We found that the high dose of 4V OT (5 {micro}g {approx} 4.96 nmol) elevated TIBAT similarly in sham mice as in denervated mice. We subsequently measured the effects of chronic 4V OT (16 nmol/day over 29 days) or vehicle infusions on body weight, adiposity and food intake in DIO mice following sham or bilateral surgical denervation of IBAT. Chronic 4V OT reduced body weight by 5.7{+/-}2.23% and 6.6{+/-}1.4% in sham and denervated mice (P<0.05), respectively, and this effect was similar between groups (P=NS). OT produced corresponding reductions in whole body fat mass (P<0.05). Together, these findings support the hypothesis that sympathetic innervation of IBAT is not necessary for OT-elicited increases in BAT thermogenesis and reductions of body weight and adiposity in male DIO mice.

pharmacology and toxicology↗

bioRxiv2024

The Novel Chimeric Multi-Agonist Peptide (GEP44) Reduces Energy Intake and Body Weight in Male and Female Diet-Induced Obese Mice in a Glucagon-Like Peptide-1 Receptor-Dependent Manner

We recently reported that a novel chimeric peptide (GEP44) targeting both the glucagon-like peptide-1 receptor (GLP-1R) and neuropeptide Y1- and Y2 receptor (Y1R and Y2R) reduced energy intake and body weight (BW) in diet-induced obese (DIO) rats. We hypothesized that GEP44 reduces energy intake and BW primarily through a GLP-1R dependent mechanism. To test this hypothesis, GLP-1R+/+ mice and GLP-1R null (GLP-1R-/-) mice were fed a high fat diet for 4 months to elicit diet-induced obesity prior to undergoing a sequential 3-day vehicle period, 3-day drug treatment (5, 10, 20 or 50 nmol/kg; GEP44 vs the selective GLP-1R agonist, exendin-4) and a 3-day washout. Energy intake, BW, core temperature and activity were measured daily. GEP44 (10, 20 and 50 nmol/kg) reduced BW after 3-day treatment in DIO male GLP-1R+/+ mice by - 1.5{+/-}0.6, -1.3{+/-}0.4 and -1.9{+/-}0.4 grams, respectively (P<0.05), with similar effects being observed in female GLP-1R+/+ mice. These effects were absent in male and female DIO GLP-1R-/- mice suggesting that GLP-1R signaling contributes to GEP44-elicited reduction of BW. Further, GEP44 decreased energy intake in both male and female DIO GLP-1R+/+ mice, but GEP44 appeared to produce more consistent effects across multiple doses in males. In GLP-1R-/- mice, the effects of GEP44 on energy intake were only observed in males and not females, suggesting that GEP44 may reduce energy intake, in part, through a GLP-1R independent mechanism in males. In addition, GEP44 reduced core temperature and activity in both male and female GLP-1R+/+ mice suggesting that it may also reduce energy expenditure. Lastly, we show that GEP44 reduced fasting blood glucose in DIO male and female mice through GLP-1R. Together, these findings support the hypothesis that the chimeric peptide, GEP44, reduces energy intake, BW, core temperature, and glucose levels in male and female DIO mice primarily through a GLP-1R dependent mechanism.

pharmacology and toxicology↗

bioRxiv2018

Mapping molecular datasets back to the brain regions they are extracted from: Remembering the native countries of hypothalamic expatriates and refugees

This article, which includes novel unpublished data along with commentary and analysis, focuses on approaches to link transcriptomic, proteomic, and peptidomic datasets mined from brain tissue to the original locations within the brain that they are derived from using digital atlas mapping techniques. We use, as an example, the transcriptomic, proteomic and peptidomic analyses conducted in the mammalian hypothalamus. Following a brief historical overview, we highlight studies that have mined biochemical and molecular information from the hypothalamus and then lay out a strategy for how these data can be linked spatially to the mapped locations in a canonical brain atlas where the data come from, thereby allowing researchers to integrate these data with other datasets across multiple scales. A key methodology that enables atlas-based mapping of extracted datasets - laser-capture microdissection - is discussed in detail, with a view of how this technology is a bridge between systems biology and systems neuroscience.

neuroscience↗