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2.
Physiol Genomics ; 54(6): 196-205, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35476598

RESUMO

The brain renin-angiotensin system (RAS) is implicated in control of blood pressure (BP), fluid intake, and energy expenditure (EE). Angiotensin II (ANG II) within the arcuate nucleus of the hypothalamus contributes to control of resting metabolic rate (RMR) and thereby EE through its actions on Agouti-related peptide (AgRP) neurons, which also contribute to EE control by leptin. First, we determined that although leptin stimulates EE in control littermates, mice with transgenic activation of the brain RAS (sRA) exhibit increased EE and leptin has no additive effect to exaggerate EE in these mice. These findings led us to hypothesize that leptin and ANG II in the brain stimulate EE through a shared mechanism. Because AgRP signaling to the melanocortin MC4R receptor contributes to the metabolic effects of leptin, we performed a series of studies examining RMR, fluid intake, and BP responses to ANG II in mice rendered deficient for expression of MC4R via a transcriptional block (Mc4r-TB). These mice were resistant to stimulation of RMR in response to activation of the endogenous brain RAS via chronic deoxycorticosterone acetate (DOCA)-salt treatment, whereas fluid and electrolyte effects remained intact. These mice were also resistant to stimulation of RMR via acute intracerebroventricular (ICV) injection of ANG II, whereas BP responses to ICV ANG II remained intact. Collectively, these data demonstrate that the effects of ANG II within the brain to control RMR and EE are dependent on MC4R signaling, whereas fluid homeostasis and BP responses are independent of MC4R signaling.


Assuntos
Angiotensina II , Metabolismo Energético , Leptina , Receptor Tipo 4 de Melanocortina , Proteína Relacionada com Agouti/metabolismo , Angiotensina II/farmacologia , Animais , Pressão Sanguínea/fisiologia , Encéfalo/metabolismo , Metabolismo Energético/fisiologia , Leptina/metabolismo , Leptina/farmacologia , Melanocortinas/metabolismo , Melanocortinas/farmacologia , Camundongos , Receptor Tipo 4 de Melanocortina/metabolismo
3.
Pediatr Blood Cancer ; 69(8): e29721, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35441478

RESUMO

Coronavirus disease 2019 (COVID-19) infection in children has been associated with thrombosis, though few cases of COVID-associated pulmonary embolism (PE) have been described. We performed a retrospective review of the nine cases of COVID-19-associated PE during the B.1617.2 variant surge at Texas Children's Hospital. The patient cohort largely contained unvaccinated obese adolescents. All patients were critically ill with two requiring catheter-directed thrombolysis in addition to anticoagulation. Eight of the nine patients had COVID pneumonia along with PE. This report stresses the importance of maintaining a high index of suspicion for PE in pediatric COVID-19 infection and vaccinating obese adolescent patients.


Assuntos
COVID-19 , Obesidade Infantil , Embolia Pulmonar , Trombose , Adolescente , COVID-19/complicações , Criança , Humanos , Embolia Pulmonar/etiologia , SARS-CoV-2 , Trombose/tratamento farmacológico , Trombose/etiologia
4.
Function (Oxf) ; 2(3): zqab019, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33939772

RESUMO

Evidence supports various roles for microbial metabolites in the control of multiple aspects of host energy flux including feeding behaviors, digestive efficiency, and energy expenditure, but few studies have quantified the energy utilization of the biomass of the gut microbiota itself. Because gut microbiota exist in an anoxic environment, energy flux is expected to be anaerobic; unfortunately, commonly utilized O2/CO2 respirometry-based approaches are unable to detect anaerobic energy flux. To quantify the contribution of the gut microbial biomass to whole-animal energy flux, we examined the effect of surgical reduction of gut biomass in C57BL/6J mice via cecectomy and assessed energy expenditure using methods sensitive to anaerobic flux, including bomb and direct calorimetry. First, we determined that cecectomy caused an acceleration of weight gain over several months due to a reduction in combined total host plus microbial energy expenditure, as reflected by an increase in energy efficiency (ie, weight gained per calorie absorbed). Second, we determined that under general anesthesia, cecectomy caused immediate changes in heat dissipation that were significantly modified by short-term pretreatment with dietary or pharmaceutical interventions known to modify the microbiome, and confirmed that these effects were undetectable by respirometry. We conclude that while the cecum only contributes approximately 1% of body mass in the mouse, this organ contributes roughly 8% of total resting energy expenditure, that this contribution is predominantly anaerobic, and that the composition and abundance of the cecal microbial contents can significantly alter its contribution to energy flux.


Assuntos
Microbioma Gastrointestinal , Microbiota , Animais , Camundongos , Biomassa , Camundongos Endogâmicos C57BL , Aumento de Peso
5.
Cell Rep ; 33(4): 108270, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33113371

RESUMO

The exact mechanisms underlying the metabolic effects of bariatric surgery remain unclear. Here, we demonstrate, using a combination of direct and indirect calorimetry, an increase in total resting metabolic rate (RMR) and specifically anaerobic RMR after Roux-en-Y gastric bypass (RYGB), but not sleeve gastrectomy (SG). We also show an RYGB-specific increase in splanchnic sympathetic nerve activity and "browning" of visceral mesenteric fat. Consequently, selective splanchnic denervation abolishes all beneficial metabolic outcomes of gastric bypass that involve changes in the endocannabinoid signaling within the small intestine. Furthermore, we demonstrate that administration of rimonabant, an endocannabinoid receptor-1 (CB1) inverse agonist, to obese mice mimics RYGB-specific effects on energy balance and splanchnic nerve activity. On the other hand, arachidonoylethanolamide (AEA), a CB1 agonist, attenuates the weight loss and metabolic signature of this procedure. These findings identify CB1 as a key player in energy regulation post-RYGB via a pathway involving the sympathetic nervous system.


Assuntos
Endocanabinoides/uso terapêutico , Derivação Gástrica/métodos , Sistema Nervoso Simpático/fisiologia , Animais , Endocanabinoides/farmacologia , Feminino , Humanos , Masculino , Camundongos
6.
Curr Hypertens Rep ; 19(4): 27, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28316052

RESUMO

PURPOSE OF REVIEW: The influence of gut bacteria upon host physiology is increasingly recognized, but mechanistic links are lacking. Diseases of energetic imbalance such as obesity and diabetes represent major risk factors for cardiovascular diseases such as hypertension. Thus, here, we review current mechanistic contributions of the gut microbiota to host energetics. RECENT FINDINGS: Gut bacteria generate a multitude of small molecules which can signal to host tissues within and beyond the gastrointestinal tract to influence host physiology, and gut bacteria can also influence host digestive efficiency by altering the bioavailability of polysaccharides, yet the quantitative energetic effects of these processes remain unclear. Recently, our team has demonstrated that gut bacteria constitute a major anaerobic thermogenic biomass, which can quantitatively account for obesity. Quantitative understanding of the mechanisms by which gut bacteria influence energy homeostasis may ultimately inform the relationship between gut bacteria and cardiovascular dysfunction.


Assuntos
Microbioma Gastrointestinal , Homeostase , Hipertensão , Animais , Doenças Cardiovasculares , Trato Gastrointestinal , Humanos , Obesidade
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