Hormonal regulation of metabolism—recent lessons learned from insulin and estrogen

Abstract

Hormonal signaling plays key roles in tissue and metabolic homeostasis. Accumulated evidence has revealed a great deal of insulin and estrogen signaling pathways and their interplays in the regulation of mitochondrial, cellular remodeling, and macronutrient metabolism. Insulin signaling regulates nutrient and mitochondrial metabolism by targeting the IRS-PI3K-Akt-FoxOs signaling cascade and PGC1α. Estrogen signaling fine-tunes protein turnover and mitochondrial metabolism through its receptors (ERα, ERβ, and GPER). Insulin and estrogen signaling converge on Sirt1, mTOR, and PI3K in the joint regulation of autophagy and mitochondrial metabolism. Dysregulated insulin and estrogen signaling lead to metabolic diseases. This article reviews the up-to-date evidence that depicts the pathways of insulin signaling and estrogen-ER signaling in the regulation of metabolism. In addition, we discuss the cross-talk between estrogen signaling and insulin signaling via Sirt1, mTOR, and PI3K, as well as new therapeutic options such as agonists of GLP1 receptor, GIP receptor, and β3-AR. Mapping the molecular pathways of insulin signaling, estrogen signaling, and their interplays advances our understanding of metabolism and discovery of new therapeutic options for metabolic disorders.

Loss of FoxO1 activates an alternate mechanism of mitochondrial quality control for healthy adipose browning

“…To further investigate how adO1KO regulates mitochondrial turnover and homeostasis, we analyzed adaptor-dependent (e.g., Pink1) and receptor-dependent (e.g., Bnip3 and Fundc1) mitophagy pathways as well as mitochondrial biogenesis (e.g., Pgc1α and Tfam) [ 6 , 16 , 42 , 43 ]. Interestingly, ablation of FoxO1 reciprocally regulated Bnip3 (down-regulated by 63%, P <0.01) and Fundc1 (up-regulated by 3.4-fold, P <0.001), although Pink1 was comparable in adO1KO and control mice ( Figure 2 A,B).…”

“…In addition, we observed the activation of FoxO3 via deacetylation (known as a stress indicator [ 48 , 49 , 54 ]) in adO1KO mice on HFD but not on chow diet (Supplementary Figure S4), supporting the notion that HFD and lipotoxicity constitute stress conditions [ 12 , 40 , 53 ]. The activation of FoxO3 may compensate for the loss of FoxO1, thereby abolishing the adO1KO-induced benefits ( Figures 4 and 5 ), in that FoxO1 and FoxO3 are redundant regulators of autophagy and mitochondria [ 6 , 16 , 17 ]. Therefore, the strategies designed to rescue lysosome function (e.g., CTSL) and silencing both FoxO transcription factors may have the potential to prevent HFD-induced metabolic disorders.…”

“…FoxO1 is a transcription factor conserved across species and has been shown to regulate mitochondria, autophagy, and metabolism [ 6 , 16 , 17 ]. Hyperactive FoxO1 in the liver dysregulates mitochondrial function and leads to metabolic disorders in mice, but ablation of FoxO1 reverses mitochondrial and metabolic abnormalities [ 18 , 19 ].…”

Effects of Weight Loss on Key Obesity-Related Biomarkers Linked to the Risk of Endometrial Cancer: A Systematic Review and Meta-Analysis

“…Leptin promotes angiogenesis by stimulating the production of vascular endothelial growth factor (VEGF), which supports tumor growth by enhancing blood supply [ 80 ]. It also activates pro-growth signaling pathways like JAK/STAT and PI3K/AKT, leading to increased cancer cell proliferation and migration [ 81 ]. Furthermore, leptin fosters a proinflammatory tumor microenvironment by increasing cytokine secretion and immune cell infiltration, which can enhance estrogen receptor activity and tumor progression [ 82 ].…”

Occurrence and sources of hormones in water resources—environmental and health impact

“…Hormones, as key regulators of biological processes, play an extremely important role in the life of aquatic organisms, as well as in the ecosystems that coexist with them (Tao and Cheng 2023 ). However, the emergence and presence of hormones in aquatic resources is becoming increasingly visible, and their sources and impacts on the environment and public health are becoming the subject of in-depth analysis and interest (Ojoghoro et al 2021 ).…”