Sulforaphane reduces obesity by reversing leptin resistance DOI Creative Commons
Işın Çakır, Pauline Lining Pan, Colleen K. Hadley

et al.

eLife, Journal Year: 2022, Volume and Issue: 11

Published: March 1, 2022

The ascending prevalence of obesity in recent decades is commonly associated with soaring morbidity and mortality rates, resulting increased health-care costs decreased quality life. A systemic state stress characterized by low-grade inflammation pathological formation reactive oxygen species (ROS) usually manifests obesity. transcription factor nuclear erythroid-derived 2-like 2 (NRF2) the master regulator redox homeostasis plays a critical role resolution inflammation. Here, we show that natural isothiocyanate potent NRF2 activator sulforaphane reverses diet-induced through predominantly, but not exclusively, NRF2-dependent mechanism requires functional leptin receptor signaling hyperleptinemia. Sulforaphane does reduce body weight or food intake lean mice induces an anorectic response when coadministered exogenous leptin. Leptin-deficient Lep ob/ob mutant Lepr db/db display resistance to weight-reducing effect sulforaphane, supporting conclusion antiobesity signaling. Furthermore, our results suggest skeletal muscle as most notable site action whose peripheral signals alleviate resistance. Transcriptional profiling six major metabolically relevant tissues highlights suppresses fatty acid synthesis while promoting ribosome biogenesis, reducing ROS accumulation, resolving inflammation, therefore representing unique transcriptional program leads protection from Our findings argue for clinical evaluation loss obesity-associated metabolic disorders.

Language: Английский

Neural mechanisms of social homeostasis DOI Creative Commons

Gillian A. Matthews,

Kay M. Tye

Annals of the New York Academy of Sciences, Journal Year: 2019, Volume and Issue: 1457(1), P. 5 - 25

Published: March 15, 2019

Social connections are vital to survival throughout the animal kingdom and dynamic across life span. There debilitating consequences of social isolation loneliness, support is increasingly a primary consideration in health care, disease prevention, recovery. Considering connection as an "innate need," it hypothesized that evolutionarily conserved neural systems underlie maintenance connections: alerting individual their absence coordinating effector mechanisms restore contact. This reminiscent homeostatic system designed maintain connection. Here, we explore identity regulating "social homeostasis." We review findings from rodent studies evaluating rapid response deficit (in form acute isolation) propose parallel, overlapping circuits engaged adapt vulnerabilities By considering other needs, such energy fluid balance, discuss potential attributes circuitry. reason uncovering these circuits/mechanisms will facilitate our understanding how loneliness perpetuates long-term states, which speculate may result sustained recruitment circuits.

Language: Английский

Citations

212
Rethinking Food Reward DOI Open Access
Ivan E. de Araújo,

Mark Schatzker,

Dana M. Small

et al.

Annual Review of Psychology, Journal Year: 2019, Volume and Issue: 71(1), P. 139 - 164

Published: Sept. 28, 2019

The conscious perception of the hedonic sensory properties caloric foods is commonly believed to guide our dietary choices. Current and traditional models implicate consciously perceived qualities food as driving overeating, whereas subliminal signals arising from gut would curb uncontrolled desire for calories. Here we review recent animal human studies that support a markedly different model reward. These findings reveal in particular existence subcortical body-to-brain neural pathways linking gastrointestinal nutrient sensors brain's reward regions. Unexpectedly, perceptible appear play less relevant, mostly transient, role reinforcement. In this model, gut-brain bypass cranial taste aroma receptors cortical networks give rise flavor perception. They instead reinforce behaviors independently cognitive processes overt insights into nature decisions.

Language: Английский

Citations

211
Brain–gut–microbiome interactions in obesity and food addiction DOI

Arpana Gupta,

Vadim Osadchiy, Emeran A. Mayer

et al.

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2020, Volume and Issue: 17(11), P. 655 - 672

Published: Aug. 27, 2020

Language: Английский

Citations

200
Arcuate Nucleus-Dependent Regulation of Metabolism—Pathways to Obesity and Diabetes Mellitus DOI Creative Commons
Alexander Jaïs,

Jens C. Brüning

Endocrine Reviews, Journal Year: 2021, Volume and Issue: 43(2), P. 314 - 328

Published: Sept. 7, 2021

Abstract The central nervous system (CNS) receives information from afferent neurons, circulating hormones, and absorbed nutrients integrates this to orchestrate the actions of neuroendocrine autonomic systems in maintaining systemic metabolic homeostasis. Particularly arcuate nucleus hypothalamus (ARC) is pivotal importance for primary sensing adiposity signals, such as leptin insulin, nutrients, glucose. Importantly, energy state–sensing neurons ARC not only regulate feeding but at same time control multiple physiological functions, glucose homeostasis, blood pressure, innate immune responses. These findings have defined them master regulators, which adapt integrative physiology state organism. disruption fine-tuned leads an imbalance between intake expenditure well deregulation peripheral metabolism. Improving our understanding cellular, molecular, functional basis regulatory principle CNS could set stage developing novel therapeutic strategies treatment obesity syndrome. In review, we summarize insights with a particular emphasis on neurocircuitries regulating food homeostasis factors that inform brain organismal status.

Language: Английский

Citations

157
Obesity remodels activity and transcriptional state of a lateral hypothalamic brake on feeding DOI Open Access
Mark A. Rossi, Marcus L. Basiri, Jenna A. McHenry

et al.

Science, Journal Year: 2019, Volume and Issue: 364(6447), P. 1271 - 1274

Published: June 27, 2019

The current obesity epidemic is a major worldwide health concern. Despite the consensus that brain regulates energy homeostasis, neural adaptations governing are unknown. Using combination of high-throughput single-cell RNA sequencing and longitudinal in vivo two-photon calcium imaging, we surveyed functional alterations lateral hypothalamic area (LHA)-a highly conserved region orchestrates feeding-in mouse model obesity. transcriptional profile LHA glutamatergic neurons was affected by obesity, exhibiting changes indicative altered neuronal activity. Encoding properties individual were then tracked throughout revealing greatly attenuated reward responses. These data demonstrate how diet disrupts function an endogenous feeding suppression system to promote overeating

Language: Английский

Citations

147
Obesity I: Overview and molecular and biochemical mechanisms DOI
Robert H. Lustig,

David Collier,

Christopher D. Kassotis

et al.

Biochemical Pharmacology, Journal Year: 2022, Volume and Issue: 199, P. 115012 - 115012

Published: April 5, 2022

Language: Английский

Citations

126
Reverse-translational identification of a cerebellar satiation network DOI
Aloysius Y. T. Low, Nitsan Goldstein,

Jessica Gaunt

et al.

Nature, Journal Year: 2021, Volume and Issue: 600(7888), P. 269 - 273

Published: Nov. 17, 2021

Language: Английский

Citations

106
Dopamine subsystems that track internal states DOI Creative Commons
James C. R. Grove, Lindsay Gray,

Naymalis La Santa Medina

et al.

Nature, Journal Year: 2022, Volume and Issue: 608(7922), P. 374 - 380

Published: July 13, 2022

Food and water are rewarding in part because they satisfy our internal needs

Language: Английский

Citations

91
Genetics and neurobiology of eating disorders DOI
Cynthia M. Bulik, Jonathan R. I. Coleman,

J. Andrew Hardaway

et al.

Nature Neuroscience, Journal Year: 2022, Volume and Issue: 25(5), P. 543 - 554

Published: May 1, 2022

Language: Английский

Citations

88
Brain functional and structural magnetic resonance imaging of obesity and weight loss interventions DOI Creative Commons
Guanya Li, Yang Hu, Wenchao Zhang

et al.

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(4), P. 1466 - 1479

Published: March 14, 2023

Abstract Obesity has tripled over the past 40 years to become a major public health issue, as it is linked with increased mortality and elevated risk for various physical neuropsychiatric illnesses. Accumulating evidence from neuroimaging studies suggests that obesity negatively affects brain function structure, especially within fronto-mesolimbic circuitry. Obese individuals show abnormal neural responses food cues, taste smell, resting-state activity functional connectivity, cognitive tasks including decision-making, inhibitory-control, learning/memory, attention. In addition, associated altered cortical morphometry, lowered gray/white matter volume, impaired white integrity. Various interventions treatments bariatric surgery, most effective treatment in clinical practice, well dietary, exercise, pharmacological, neuromodulation such transcranial direct current stimulation, magnetic stimulation neurofeedback have been employed achieved promising outcomes. These appear normalize hyper- hypoactivations of regions involved reward processing, food-intake control, function, also promote recovery structural abnormalities. This paper provides comprehensive literature review recent advances on underlying mechanisms both interventions, hope guiding development novel treatments.

Language: Английский

Citations

64