Activation of POMC neurons to adiponectin participating in EA-mediated improvement of high-fat diet IR mice

Abstract

BackgroundInsulin resistance (IR) is one of the common pathological manifestations of metabolic-related diseases, and the prevalence of relevant diseases is high. Acupuncture is beneficial to IR patients, but the central mechanism underlying this treatment remains unclear. This study provides mechanistic insights into how electroacupuncture (EA) improves IR through the response of Pro-opiomelanocortin (POMC) neurons to adiponectin (Adipo).MethodsGlucose tolerance tests (GTT), Insulin tolerance tests (ITT) and fasting blood glucose (FBG) were detected by glucometer. Serum insulin, Adipo and skeletal muscle adiponectin receptor 1 (AdipoR1) protein levels were examined by ELISA. Homeostasis model assessment estimated insulin resistance (HOMA-IR) was calculated using the following formula: HOMA-IR = fasting insulin (FINS) (mU/L) × FBG (mmol/L)/22.5. The expression levels of AdipoR1 and Adipo mRNA in skeletal muscle were detected by real-time PCR quantification. The co-marking of c-Fos/AdipoR1 and POMC neurons were investigated using immunofluorescence. Spontaneous excitatory postsynaptic currents (sEPSCs) of POMC neurons and the response of POMC neurons to Adipo were detected via electrophysiology.ResultsEA significantly ameliorated HFD-induced impairment of GTT, ITT, FBG, and HOMA-IR which was correlated with recovery of the expression level of AdipoR1 and Adipo in skeletal muscle. The improved response of POMC neurons to Adipo in the hypothalamus may be a key factor in correcting abnormal glucose tolerance and improving IR.ConclusionThis study demonstrates that EA can ameliorate HFD-induced impaired glucose tolerance through improved response of POMC neurons to Adipo in the hypothalamus, providing insight into the central mechanism of improving IR through EA.

Pharmacological activation of insulin‐degrading enzyme improves insulin secretion and glucose tolerance in diet‐induced obese mice

“…To further decipher the mechanism(s) by which sPIF improves insulin secretion in β‐cells, we assessed GSIS in Min‐6 cells in the absence or the presence of 6bK (10 μM, 30 minutes), a highly specific inhibitor of IDE activity 29,35 . As shown in Figure 3A,B, 6bK treatment did not affect GSIS.…”

“…To determine hepatic insulin clearance, the molar ratio C‐peptide/insulin was calculated from fasting insulin and C‐peptide levels, as previously described 25 . The homeostatic model assessment (HOMA) index was calculated using fasting insulin and glucose concentrations, according to 26–29 …”

The contribution of the nervous system in the cancer progression

“…The hypothalamic proopiomelanocortin (POMC) neurons play a crucial role in appetite suppression and activation of energy metabolism through SNS activation ( 98 ). Various studies have been conducted over the last decades to combat obesity and metabolic disorders by enhancing the activity of POMC neurons ( 98 - 100 ). Indeed, α-melanocyte stimulating hormone (MSH), one of derivatives of POMC precursor, significantly enhance the symapthetic activity by binding to and activating MC-4 receptor in paraventricular hypothalamus ( 101 ).…”

Comprehensive landscape-style investigation of the molecular mechanism of acupuncture at ST36 single acupoint on different systemic diseases

“…It also improves insulin sensitivity. Moreover, the regulation of insulin resistance by electroacupuncture ST36 may be related to Pro-opiomelanocortin (POMC) neurons in the hypothalamus, which are able to activate the adiponectin (Adipo) response in skeletal muscle to regulate glucose metabolism [ 104 ]. This is important because the brain relies on glucose as its main source of energy.…”