The Role of Estrogen in Insulin Resistance

Paoli, Monica De; Zakharia, Alexander; Werstuck, Geoff H.

doi:10.1016/j.ajpath.2021.05.011

Cited by 110 publications

(64 citation statements)

References 84 publications

(128 reference statements)

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“…Both age-related and surgically induced menopause increase insulin resistance and the prevalence of other components of the metabolic syndrome [ 112 ]. These findings suggest the role of estrogen in the regulation of responsiveness to insulin [ 113 ]. However, the results of the studies evaluating the influence of HRT on glucose metabolism are not univocal which may be a consequence of methodological differences regarding the population selection, HRT type, and regimen as well as the timing of treatment initiation [ 114 ].…”

Section: Estrogens In the Regulation Of Adipose Tissue Metabolismmentioning

confidence: 99%

Estrogens in Adipose Tissue Physiology and Obesity-Related Dysfunction

Kuryłowicz

2023

Biomedicines

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Menopause-related decline in estrogen levels is accompanied by a change in adipose tissue distribution from a gynoid to an android and an increased prevalence of obesity in women. These unfavorable phenomena can be partially restored by hormone replacement therapy, suggesting a significant role for estrogen in the regulation of adipocytes’ function. Indeed, preclinical studies proved the involvement of these hormones in adipose tissue development, metabolism, and inflammatory activity. However, the relationship between estrogen and obesity is bidirectional. On the one hand-their deficiency leads to excessive fat accumulation and impairs adipocyte function, on the other-adipose tissue of obese individuals is characterized by altered expression of estrogen receptors and key enzymes involved in their synthesis. This narrative review aims to summarize the role of estrogen in adipose tissue development, physiology, and in obesity-related dysfunction. Firstly, the estrogen classification, synthesis, and modes of action are presented. Next, their role in regulating adipogenesis and adipose tissue activity in health and the course of obesity is described. Finally, the potential therapeutic applications of estrogen and its derivates in obesity treatment are discussed.

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Section: Estrogens In the Regulation Of Adipose Tissue Metabolismmentioning

confidence: 99%

Estrogens in Adipose Tissue Physiology and Obesity-Related Dysfunction

Kuryłowicz

2023

Biomedicines

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“…Male LVR also had significantly higher bodyweights relative to age-matched WT ( p = 0.031) ( Figure 6D ). This indicates that male LVR show signs of insulin resistance and obesity likely increasing their risk for AD while female LVR, relative to same-sex controls, were relatively unaffected potentially due to the protective effects of estrogen in the periphery ( de Paoli et al, 2021 ). We see very distinct effects of selecting for physical inactivity between male and female LVR in which female LVR primarily display significant deficits in brain health; whereas male LVR display systemic issues like insulin resistance and obesity yet are relatively spared from cognitive deficits.…”

Section: Resultsmentioning

confidence: 99%

Selective breeding for physical inactivity produces cognitive deficits via altered hippocampal mitochondrial and synaptic function

Kerr

Kelty

Mao

et al. 2023

Front. Aging Neurosci.

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Physical inactivity is the 4th leading cause of death globally and has been shown to significantly increase the risk for developing Alzheimer’s Disease (AD). Recent work has demonstrated that exercise prior to breeding produces heritable benefits to the brains of offspring, suggesting that the physical activity status of previous generations could play an important role in one’s brain health and their subsequent risk for neurodegenerative diseases. Thus, our study aimed to test the hypothesis that selective breeding for physical inactivity, or for high physical activity, preference produces heritable deficits and enhancements to brain health, respectively. To evaluate this hypothesis, male and female sedentary Low Voluntary Runners (LVR), wild type (WT), and High Voluntary Runner (HVR) rats underwent cognitive behavioral testing, analysis of hippocampal neurogenesis and mitochondrial respiration, and molecular analysis of the dentate gyrus. These analyses revealed that selecting for physical inactivity preference has produced major detriments to cognition, brain mitochondrial respiration, and neurogenesis in female LVR while female HVR display enhancements in brain glucose metabolism and hippocampal size. On the contrary, male LVR and HVR showed very few differences in these parameters relative to WT. Overall, we provide evidence that selective breeding for physical inactivity has a heritable and detrimental effect on brain health and that the female brain appears to be more susceptible to these effects. This emphasizes the importance of remaining physically active as chronic intergenerational physical inactivity likely increases susceptibility to neurodegenerative diseases for both the inactive individual and their offspring.

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“…There is compelling data in men that testosterone deficiency predisposed to MetS and in females that estrogen deficiency predisposes to an increase risk of MetS. 30 , 31 Furthermore studies have shown that sex hormone binding globulin (SHBG) also is an important determinant of MetS risk. 32 , 33 In future studies this important area needs to be investigated in relationship to insulin resistance and inflammation and dysbiosis of gut microbiota.…”

Section: Discussionmentioning

confidence: 99%

Correlates of Insulin Resistance in Nascent Metabolic Syndrome

Adams‐Huet

Jialal

2023

Clin Med Insights Endocrinol Diabetes

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Background: Metabolic Syndrome (MetS), a major global problem, is a cluster of cardio-metabolic risk factors that predisposes to both type 2 diabetes mellitus (T2DM) and premature atherosclerotic cardiovascular disease (ASCVD). Insulin resistance is a major underpinning of MetS. Objectives: We investigated the relationship between insulin resistance and biomarkers of inflammation, oxidative stress, free fatty acids (FFA) levels and adipokine dysregulation in a cohort of nascent MetS. Design: This was a cross-sectional study comparing patients with MetS with matched controls. Patients and Methods: Participants included 47 patients with MetS and 41 controls. Persons with diabetes, ASCVD, smoking and macro-inflammation were excluded. Fasting blood was obtained for both plasma and monocyte isolation. Homeostasis model assessment insulin resistance index (HOMA-IR) was calculated from fasting glucose and insulin levels. Results: The patients were insulin resistant as determined by a valid measure, HOMA-IR. HOMA-IR increased with increasing severity of MetS and correlated with cardio-metabolic features, hsCRP, FFA levels, and adipose tissue insulin resistance. Insulin resistance also correlated with biomarkers of oxidative stress and both circulating and cellular biomarkers of inflammation. Receiver operating Characteristic (ROC) curve analysis revealed that HOMA-IR was an excellent predictor of MetS with an area under the curve of 0.80. Conclusion: In our patients with nascent MetS we show that they have significant insulin resistance. Based on our findings, elevated FFA levels, oxidative stress and inflammation could contribute to the insulin resistance.

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The Role of Estrogen in Insulin Resistance

Cited by 110 publications

References 84 publications

Estrogens in Adipose Tissue Physiology and Obesity-Related Dysfunction

Estrogens in Adipose Tissue Physiology and Obesity-Related Dysfunction

Selective breeding for physical inactivity produces cognitive deficits via altered hippocampal mitochondrial and synaptic function

Correlates of Insulin Resistance in Nascent Metabolic Syndrome

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