A5001215172- Adipose Tissue and Metabolism
- Renin-Angiotensin System Studies
- Receptor Mechanisms and Signaling
- Regulation of Appetite and Obesity
- Genetics, Aging, and Longevity in Model Organisms
- Cardiovascular Disease and Adiposity
- Circadian rhythm and melatonin
- Neuroendocrine regulation and behavior
- Nutrition, Genetics, and Disease
- Birth, Development, and Health
- Cancer, Hypoxia, and Metabolism
- Anesthesia and Neurotoxicity Research
- Advanced Chemical Sensor Technologies
- MicroRNA in disease regulation
- Peroxisome Proliferator-Activated Receptors
- Heart Rate Variability and Autonomic Control
- Diet and metabolism studies
- Adipokines, Inflammation, and Metabolic Diseases
- Sodium Intake and Health
- Biochemical Analysis and Sensing Techniques
- Hops Chemistry and Applications
- Electrolyte and hormonal disorders
- Hormonal Regulation and Hypertension
Scripps Research Institute
2018-2024
Molecular Medicine Research Institute
2018
University of Iowa
2012-2017
Fraternal Order of Eagles
2015
Nicolet Chartrand Knoll (Canada)
2014-2015
Extracts of the hops plant have been shown to reduce weight and insulin resistance in rodents humans, but elucidation mechanisms responsible for these benefits has hindered by use heterogeneous hops-derived mixtures. Because hop extracts are used as flavoring agents their bitter properties, we hypothesized that taste receptors (Tas2rs) could be mediating beneficial effects metabolic disease. Studies exposure cultured enteroendocrine cells tastants can stimulate release hormones, including...
Leptin contributes to the control of resting metabolic rate (RMR) and blood pressure (BP) through its actions in arcuate nucleus (ARC). The renin-angiotensin system (RAS) angiotensin AT1 receptors within brain are also involved RMR BP, but whether this regulation overlaps with leptin’s is unclear. Here, we have demonstrated selective requirement AT1A receptor leptin-mediated RMR. We observed that colocalized leptin (LEPRs) ARC. Cellular coexpression LEPR was almost exclusive ARC occurred...
An indispensable role for the brain renin-angiotensin system (RAS) has been documented in most experimental animal models of hypertension. To identify specific efferent pathway activated by RAS that mediates hypertension, we examined hypothesis elevated arginine vasopressin (AVP) release is necessary hypertension a double-transgenic model brain-specific hyperactivity (the “sRA” mouse model). sRA mice experience activity due to human angiotensinogen expression plus neuron-specific renin...
Activation of the brain renin-angiotensin system (RAS) stimulates energy expenditure through increasing resting metabolic rate (RMR), and this effect requires simultaneous suppression circulating and/or adipose RAS. To identify mechanism by which peripheral RAS opposes RMR control RAS, we examined mice with transgenic activation (sRA mice). sRA exhibit increased flux in inguinal tissue, is attenuated angiotensin II type 2 receptor (AT2) activation. AT2 adipocytes norepinephrine-induced...
The mechanisms by which the sensory environment influences metabolic homeostasis remains poorly understood. In this report, we show that oxygen, a potent environmental signal, is an important regulator of whole body lipid metabolism. C. elegans oxygen-sensing neurons reciprocally regulate peripheral metabolism under normoxia in following way: high oxygen and food absence, URX are activated, stimulate fat loss intestine, major organ for elegans. Under lower conditions or when present, BAG...
Abstract Dietary fats and sodium are both palatable hypothesized to synergistically contribute ingestive behavior thereby obesity. Contrary this hypothesis, C57BL/6J mice fed a 45% high fat diet exhibited weight gain that was inhibited by increased dietary content. This suppressive effect of upon mediated specifically through reduction in digestive efficiency, with no effects on food intake behavior, physical activity, or resting metabolism. Replacement circulating angiotensin II levels...
The relationship between lipid metabolism and longevity remains unclear. Although fat oxidation is essential for weight loss, whether it beneficial when sustained long periods, the extent to which may attenuate or augment lifespan remain important unanswered questions. Here, we develop an experimental handle in Caenorhabditis elegans model system, uncover mechanisms that connect long-term with longevity. We find β-oxidation via activation of conserved triglyceride lipase ATGL-1, triggers a...
The brain-specific isoform of renin (Ren-b) has been proposed as a negative regulator the brain renin–angiotensin system (RAS). We analyzed mice with selective deletion Ren-b which preserved expression classical (Ren-a) isoform. reported that Null exhibited central RAS activation and hypertension through increased Ren-a, but dipsogenic metabolic effects in are unknown. Fluid intake was similar control at baseline both an equivalent response to deoxycorticosterone acetate–salt. Dehydration...
In C. elegans mechanisms by which peripheral organs relay internal state information to the nervous system remain unknown, although strong evidence suggests that such signals do exist. Here we report discovery of a peptide ancestral insulin superfamily called INS-7 functions as an enteroendocrine and is secreted from specialized cells intestine. secretion stimulated food withdrawal, increases during fasting acts bona fide gut-to-brain attenuates release neuropeptide drives fat loss in...
The renin‐angiotensin system (RAS) contributes to metabolic control through local actions within the brain and adipose. All components of RAS are also expressed in gastro‐intestinal (GI) tract, leading hypothesis that controls digestive efficiency. Mice with transgenic hyperactivity (sRA) were generated neuron‐specific expression human renin, angiotensinogen via its own promoter. sRA exhibit reduced body mass elevated resting rate sympathetic nervous activity a chronic suppression...
The brain Renin‐Angiotensin System (RAS) plays an important role in the regulation of metabolic function. While ACE2 has been reported to modulate RAS activity, its central metabolism is unknown. To determine metabolism, Body weight and intake behaviors, assessed using cages, were measured 24 wk old non‐transgenic (NT, n=8) transgenic mice overexpressing (SA, n=8). Fasting blood glucose was after a 14 h overnight fasting. Glucose tolerance test performed by measuring at 15, 30, 60 120 min IP...
Transgenic “sRA” mice with brain renin‐angiotensin system hyperactivity express human renin via the synapsin promoter and angiotensinogen its own promoter. These exhibit an elevated resting metabolic rate (RMR) that is normalized by replacement of circulating angiotensin II (ANG), but thermogenic tissue ANG receptors involved are unknown. sRA exhibited a robust specific elevation in uncoupling protein 1 (UCP1) expression glucose uptake inguinal adipose tissue. Chronic infusion AT 2 receptor...
The renin-angiotensin system (RAS) contributes to energy balance through opposing actions in the brain and periphery. We hypothesize that tissue- receptor-specific RAS modulation may represent a novel therapeutic approach obesity. Transgenic “sRA” mice exhibit brain-specific hyperactivity expression of human renin neurons (synapsin promoter) angiotensinogen via its own promoter. Previously we documented sRA suppressed circulating RAS, an elevated resting metabolic rate (RMR) is sensitive...
The renin-angiotensin system (RAS) positively correlates with obesity, and contributes to energy homeostasis through opposing actions in the brain adipose. We hypothesize that site- receptor-specific modulation may represent a novel therapeutic target for obesity. Transgenic “sRA” mice exhibit brain-specific RAS hyperactivity expression of human renin neurons (synapsin promoter) angiotensinogen via its own promoter. Previously we documented sRA suppressed circulating RAS, an elevated resting...
Renin gene expression is regulated by two distinct promoter-first exon combinations that target renin for either secretion (exon 1a initiating secreted renin, sREN) or cytoplasmic retention 1b intracellular icREN). The icREN isoform expressed predominantly in the brain and its downregulated whereas sREN upregulated deoxycorticosterone (DOCA)-salt suggesting each may be differentially regulated. We generated mice conditionally lack icREN, but preserve sREN, targeting a novel allele ES cells...
The brain renin-angiotensin system (RAS) stimulates resting metabolic rate (RMR) in part through a mechanism involving suppression of the circulating RAS. This effect appears to be mediated loss tonic adipose angiotensin AT2 receptor (AT2R) activation specifically within inguinal fat. Mice with hyperactivity RAS (“sRA” mice, expressing human renin via synapsin promoter and angiotensinogen its own promoter) littermate controls were chronically infused vehicle or AT2R agonist, CGP-42112a (CGP,...
To examine the synergistic effects of dietary sodium and fat on weight gain, male C57Bl/6J mice (9 wk) were placed (n=5 each) a 45% (kcal) high‐fat diet (HFD, Bio‐Serv) with 0.25, 0.5, 1, 2, or 4% sodium, standard chow (Teklad 7013). While baseline body masses indistinguishable, rate gain was increased HFD, this reduced increasing content (chow = 0.52±0.02, vs HFD+0.25% 1.88±0.17, HFD+4% 0.70±0.10 g/week). NMR at 4 weeks revealed adipose mass gains that paralleled gains, preventing in...
Transgenic “sRA” mice with hyperactivity of the brain renin‐angiotensin system (RAS) express human renin via synapsin promoter and angiotensinogen its own promoter. sRA exhibit increased resting metabolic rate (RMR) due to reduced activation adipose angiotensin AT2 receptors. To identify downstream pathways, RNA‐Seq was performed using inguinal from littermate controls, or without infusion agonist CGP‐42112a (“CGP,” 50 ng/kg/min, s.c.). In vs there were significant expression changes in 123...
Renin gene expression is regulated by two distinct promoter / first exon combinations that target renin for either secretion (exon 1a) or cytoplasmic retention 1b). Renin‐1b expressed predominantly in the brain and differentially from renin‐1a response to stimuli such as deoxycorticosterone (DOCA)‐salt. Mice were generated lack 1b (and thereby intracellular renin, icREN‐KO) but retain 1a. Male icREN‐KO mice similar size (n=4, 14.7±0.9 wk, 27.94±1.08 g) compared littermate controls (n=7,...
The effect of hyperactivity the brain renin‐angiotensin system (RAS) on metabolism was explored using double‐transgenic “sRA” mice, which express human renin via synapsin promoter and angiotensinogen its own promoter. sRA mice exhibit hypertension, polydipsia, elevated resting metabolic rate (RMR). Compared to control littermates (n=9), body mass lower in (n=9) (25.11±1.26 vs 18.95±0.87 g, P<0.05), i.p. glucose tolerance (ipGTT, 2 g/kg total body) improved (genotype x time P=0.03). Lean...
The brain renin-angiotensin system (RAS) modulates blood pressure and resting metabolic rate (RMR). Double-transgenic “sRA” mice exhibit brain-specific elevations in RAS activity, as a human renin transgene is expressed via the neuron-specific synapsin promoter angiotensinogen its own promoter. sRA have significantly lower body weight due primarily to increased RMR, which sustained through chronically sympathetic nerve activity (SNA) hypertension-mediated suppression of circulating RAS. Here...
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