- •sEV-mediated systemic targeting of AMPKα1 in SF1 neurons reduces AMPK activity, specifically in the VMH.
- •Systemic SF1-AMPKα1-DN sEVs induce feeding-independent weight loss in leptin receptor deficient db/db mice.
- •Systemic SF1-AMPKα1-DN sEVs increased SNS tone and BAT thermogenesis in leptin receptor deficient db/db mice.
- •Systemic SF1-AMPKα1-DN sEVs increased WAT browning in leptin receptor deficient db/db mice.
Background and aims
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- Novel noninvasive approaches to the treatment of obesity: from pharmacotherapy to gene therapy.Endocr Rev. 2022; 43: 507-557
- The genetics of obesity: from discovery to biology.Nat Rev Genet. 2022; 23: 120-133
- Anti-obesity drug discovery: advances and challenges.Nat Rev Drug Discov. 2022; 21: 201-223
- MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency.Nat Med. 2018; 24: 551-555
- Proopiomelanocortin deficiency treated with a Melanocortin-4 receptor agonist.N Engl J Med. 2016; 375: 240-246
- Melanocortin 4 receptor mutations become common.Cell Metab. 2021; 33: 1512-1513
- Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials.Lancet Diabetes Endocrinol. 2020; 8: 960-970
- Hypothalamic AMPK as a possible target for energy balance-related diseases.Trends Pharmacol Sci. 2022; 43: 546-556
- Hypothalamic AMPK: a canonical regulator of whole-body energy balance.Nat Rev Endocrinol. 2016; 12: 421-432
- AMP-activated protein kinase plays a role in the control of food intake.J Biol Chem. 2004; 279: 12005-12008
- AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus.Nature. 2004; 428: 569-574
- Involvement of hypothalamic AMP-activated protein kinase in leptin-induced sympathetic nerve activation.PLoS ONE. 2013; 8e56660
- SF1-specific AMPKalpha1 deletion protects against diet-induced obesity.Diabetes. 2018; 67: 2213-2226
- Small extracellular vesicle-mediated targeting of hypothalamic AMPKalpha1 corrects obesity through BAT activation.Nat Metab. 2021; 3: 1415-1431
- Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes.Nat Biotechnol. 2011; 29: 341-345
- Hypothalamic AMPK-ER stress-JNK1 Axis mediates the central actions of thyroid hormones on energy balance.Cell Metab. 2017; 26e12
- Estradiol regulates energy balance by ameliorating hypothalamic ceramide-induced ER stress.Cell Rep. 2018; 25: 413-423
- Central nicotine induces browning through hypothalamic kappa opioid receptor.Nat Commun. 2019; 10: 4037
- Activation of hypothalamic AMPK ameliorates metabolic complications of experimental arthritis.Arthritis Rheumatol. 2022; 74: 212-222
- BMP8 and activated brown adipose tissue in human newborns.Nat Commun. 2021; 12: 5274
- Reduction of hypothalamic ER stress activates Browning of white fat and ameliorates obesity.Diabetes. 2017; 66: 87-99
- Olfactomedin 2 deficiency protects against diet-induced obesity.Metabolism. 2022; 155122
- Fitting linear mixed-effects models using lme4.J Stat Softw. 2015; 67: 1-48
- emmeans: Estimated Marginal Means, aka Least-Squares Means. R package version 1.5.1.0005.2020
- R: A Language and Environment for Statistical Computing.2020
- Leptin-induced sympathetic nerve activation: signaling mechanisms and cardiovascular consequences in obesity.Curr Hypertens Rev. 2010; 6: 104-209
- A functional link between AMPK and orexin mediates the effect of BMP8B on energy balance.Cell Rep. 2016; 16: 2231-2242
- Thyroid hormones induce browning of white fat.J Endocrinol. 2017; 232: 351-362
- Effects of recombinant leptin therapy in a child with congenital leptin deficiency.N Engl J Med. 1999; 341: 879-884
- 20 years of leptin: human disorders of leptin action.J Endocrinol. 2014; 223: T63-T70