Neuronal modulation of hepatic lipid accumulation induced by bingelike drinking

Abstract

Excessive alcohol consumption, including binge drinking, is a common cause of fatty liver disease. Binge drinking rapidly induces hepatic steatosis, an early step in the pathogenesis of chronic liver injury. Despite its prevalence, the process by which excessive alcohol consumption promotes hepatic lipid accumulation remains unclear. Alcohol exerts potent effects on the brain, including hypothalamic neurons crucial for metabolic regulation. However, whether or not the brain plays a role in alcohol-induced hepatic steatosis is unknown. In the brain, alcohol increases extracellular levels of adenosine, a potent neuromodulator, and previous work implicates adenosine signaling as being important for the development of alcoholic fatty liver disease. Acute alcohol exposure also increases both the activity of agouti-related protein (AgRP)-expressing neurons and AgRP immunoreactivity. Here, we show that adenosine receptor A2B signaling in the brain modulates the extent of alcohol-induced fatty liver in mice and that both the AgRP neuropeptide and the sympathetic nervous system are indispensable for hepatic steatosis induced by bingelike alcohol consumption. Together, these results indicate that the brain plays an integral role in alcohol-induced hepatic lipid accumulation and that central adenosine signaling, hypothalamic AgRP, and the sympathetic nervous system are crucial mediators of this process.

Alternative adenosine Receptor activation: The netrin-Adora2b link

“…Hepatic ischemia and reperfusion injury occurs during major liver surgery, or during liver transplantation, and represents a major hurdle towards improving outcomes in these clinical scenarios (Ju et al, 2016;Lee et al, 2020a;Cata et al, 2020;Conrad and Eltzschig, 2020). Previous studies had implicated hypoxia-signaling in liver protection, and provided a strong rationale for exploring the netrin-Adora2b link during hepatic ischemia and reperfusion injury (Eltzschig et al, 2009b;Gao et al, 2020;Ibars et al, 2020;Wang et al, 2021a;Ju et al, 2021;Kim et al, 2021). In this context it is not surprising that studies in mice with partial netrin-1 deletion (Ntn1 +/− ) experienced lower efficacy in reducing neutrophil infiltration, had lower levels of pro-inflammatory cytokines, and exhibited attenuated liver injury during hepatic ischemia/reperfusion injury compared to wildtype control animals (Schlegel et al, 2016).…”

Implantable Triboelectric Nanogenerators for Self‐Powered Cardiovascular Healthcare

“…[ 141–143 ] Furthermore, such an I‐TENG‐based monitoring system could be expanded to other cardiovascular‐related diseases, such as diabetes and obesity, as well as to daily monitoring of patients’ diet, alcohol consumption, and other metabolic factors in the prevention and proactive treatment of cardiovascular diseases. [ 144–150 ]…”

“…[141][142][143] Furthermore, such an I-TENG-based monitoring system could be expanded to other cardiovascular-related diseases, such as diabetes and obesity, as well as to daily monitoring of patients' diet, alcohol consumption, and other metabolic factors in the prevention and proactive treatment of cardiovascular diseases. [144][145][146][147][148][149][150] For the cardiovascular healthcare systems, as reviewed in the previous sections, implantable self-powered therapeutic devices provide promising aspects within the ever-evolving IoT and the ever-increasing demand for personalized healthcare [151] (Figure 7a). Such point-to-point care system tackles the issue of time and money consuming of traditional cardiovascular healthcare systems.…”

Oxidative Stress: A Suitable Therapeutic Target for Optic Nerve Diseases?

“…This field is continuously evolving, not only for the retina but also for other ocular structures, such as the cornea and ciliary body [464]. Moreover, it extends beyond ophthalmology, finding applications in fields like cardiology and the peripheral nervous system [465][466][467][468][469]. Retinal ultrasound stimulation is a promising therapeutic approach for TON [470].…”