FOXO1 is regulated by insulin and IGF1 in pituitary gonadotropes

Skarra, Danalea V.; Thackray, Varykina G.

doi:10.1016/j.mce.2015.02.006

Cited by 16 publications

(5 citation statements)

References 84 publications

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“…Moreover, FoxO1 activity can be regulated by in vivo and in vitro growth factors and stress factors [ 43 ]. In response to growth factors such as FSH, IGF-1, glucose, and insulin, protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) can phosphorylate FoxO1, inducing FoxO1 interaction with chaperone proteins 14-3-3 and causing its cytoplasmic retention [ 41 , 44 , 45 ]. In response to oxidative stress, c-Jun N-terminal protein kinases (JNK), known as stress-activated protein kinases, are activated by oxidative stress [ 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Critical Role of FoxO1 in Granulosa Cell Apoptosis Caused by Oxidative Stress and Protective Effects of Grape Seed Procyanidin B2

Zhang

Gao

Wang

et al. 2016

Oxidative Medicine and Cellular Longevity

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Reactive oxygen species (ROS) are closely related to the follicular granulosa cell apoptosis. Grape seed procyanidin B2 (GSPB2) has been reported to possess potent antioxidant activity. However, the GSPB2-mediated protective effects and the underlying molecular mechanisms in granulosa cell apoptosis process remain unknown. In this study, we showed for the first time that GSPB2 treatment decreased FoxO1 protein level, improved granulosa cell viability, upregulated LC3-II protein level, and reduced granulosa cell apoptosis rate. Under a condition of oxidative stress, GSPB2 reversed FoxO1 nuclear localization and increased its level in cytoplasm. In addition, FoxO1 knockdown inhibited the protective effects of GSPB2 induced. Our findings suggest that FoxO1 plays a pivotal role in regulating autophagy in granulosa cells, GSPB2 exerts a potent and beneficial role in reducing granulosa cell apoptosis and inducing autophagy process, and targeting FoxO1 could be significant in fighting against oxidative stress-reduced female reproductive system diseases.

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Section: Discussionmentioning

confidence: 99%

Critical Role of FoxO1 in Granulosa Cell Apoptosis Caused by Oxidative Stress and Protective Effects of Grape Seed Procyanidin B2

Zhang

Gao

Wang

et al. 2016

Oxidative Medicine and Cellular Longevity

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“… 51 Insulin and IGF-1 act as negative regulators of FoxO1 activity and enhance gonadotropin expression. 52 Increased insulin/IGF-1 signaling of Western diet thus promotes the synthesis of pituitary gonadotropins, which are pivotal stimuli for gonadal steroidogenesis.…”

Section: Igf-1 Inhibits Foxo1 Signaling At Multiple Regulatory Layersmentioning

confidence: 99%

Linking diet to acne metabolomics, inflammation, and comedogenesis: an update

Melnik¹

2015

CCID

197

177

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Acne vulgaris, an epidemic inflammatory skin disease of adolescence, is closely related to Western diet. Three major food classes that promote acne are: 1) hyperglycemic carbohydrates, 2) milk and dairy products, 3) saturated fats including trans-fats and deficient ω-3 polyunsaturated fatty acids (PUFAs). Diet-induced insulin/insulin-like growth factor (IGF-1)-signaling is superimposed on elevated IGF-1 levels during puberty, thereby unmasking the impact of aberrant nutrigenomics on sebaceous gland homeostasis. Western diet provides abundant branched-chain amino acids (BCAAs), glutamine, and palmitic acid. Insulin and IGF-1 suppress the activity of the metabolic transcription factor forkhead box O1 (FoxO1). Insulin, IGF-1, BCAAs, glutamine, and palmitate activate the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1), the key regulator of anabolism and lipogenesis. FoxO1 is a negative coregulator of androgen receptor, peroxisome proliferator-activated receptor-γ (PPARγ), liver X receptor-α, and sterol response element binding protein-1c (SREBP-1c), crucial transcription factors of sebaceous lipogenesis. mTORC1 stimulates the expression of PPARγ and SREBP-1c, promoting sebum production. SREBP-1c upregulates stearoyl-CoA- and Δ6-desaturase, enhancing the proportion of monounsaturated fatty acids in sebum triglycerides. Diet-mediated aberrations in sebum quantity (hyperseborrhea) and composition (dysseborrhea) promote Propionibacterium acnes overgrowth and biofilm formation with overexpression of the virulence factor triglyceride lipase increasing follicular levels of free palmitate and oleate. Free palmitate functions as a “danger signal,” stimulating toll-like receptor-2-mediated inflammasome activation with interleukin-1β release, Th17 differentiation, and interleukin-17-mediated keratinocyte proliferation. Oleate stimulates P. acnes adhesion, keratinocyte proliferation, and comedogenesis via interleukin-1α release. Thus, diet-induced metabolomic alterations promote the visible sebofollicular inflammasomopathy acne vulgaris. Nutrition therapy of acne has to increase FoxO1 and to attenuate mTORC1/SREBP-1c signaling. Patients should balance total calorie uptake and restrict refined carbohydrates, milk, dairy protein supplements, saturated fats, and trans-fats. A paleolithic-like diet enriched in vegetables and fish is recommended. Plant-derived mTORC1 inhibitors and ω-3-PUFAs are promising dietary supplements supporting nutrition therapy of acne vulgaris.

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“…IGF‐1 in human males is thought to be stimulated by gonadotropins (Grizard, ) and more specifically by follicle‐stimulating hormone (FSH) and testosterone (Itoh et al., ). IGF‐1, in its turn, regulates forkhead box protein O1 (FOXO1) which downregulates production of gonadotropins (Skarra & Thackray, ).…”

Section: Introductionmentioning

confidence: 99%

Association between male Infertility and seminal plasma levels of growth hormone and insulin-like growth factor-1

et al. 2018

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Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) have been proposed to play a pivotal role in male infertility due to their anabolic effects. The aim of this study was to investigate possible associations between seminal plasma levels of GH and IGF-1 and sperm parameters. Fifty men participated in this study. Semen analysis was performed, while cell-free seminal plasma was collected following sperm centrifugation. Seminal plasma concentrations of IGF-1 and GH were determined by enzyme-linked immunosorbent assay (ELISA). Due to the presence of asthenozoospermia in all participants who presented with abnormal sperm parameters, the participants were further subdivided into normal (group A), asthenozoospermic (group B) and asthenozoospermic plus at least one additional abnormal parameter (group C). A marginally nonsignificant statistical difference (p = 0.063) was revealed between the GH levels corresponding to the asthenozoospermic and the normal group with the latter presenting with higher GH levels. A statistically significant positive correlation (p < 0.05) was noted between levels of GH and IGF-1 in group C. The above relationship has also been observed in men with low sperm concentration, vitality, volume and abnormal morphology. These novel findings require further investigation in order for the biological significance of those associations to be clarified.

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FOXO1 is regulated by insulin and IGF1 in pituitary gonadotropes

Cited by 16 publications

References 84 publications

Critical Role of FoxO1 in Granulosa Cell Apoptosis Caused by Oxidative Stress and Protective Effects of Grape Seed Procyanidin B2

Critical Role of FoxO1 in Granulosa Cell Apoptosis Caused by Oxidative Stress and Protective Effects of Grape Seed Procyanidin B2

Linking diet to acne metabolomics, inflammation, and comedogenesis: an update

Association between male Infertility and seminal plasma levels of growth hormone and insulin-like growth factor-1

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