Abstract:Background
Obesity and adult weight gain are linked to increased breast cancer risk and poorer clinical outcomes in postmenopausal women, particularly for hormone-dependent tumors. Menopause is a time when significant weight gain occurs in many women, and clinical and preclinical studies have identified menopause (or ovariectomy) as a period of vulnerability for breast cancer development and promotion.
Methods
We hypothesized that preventing weigh… Show more
“…This study was done on NOVX and OVX rats in an attempt to clarify this. It is well known that ovariectomy induces weight gain (Wellberg, 2022). Similarly in the present study, bilateral ovariectomy resulted in an increase in the body weight of rats, which was not affected by the 4week administration of sertraline.…”
Background: Selective serotonin reuptake inhibitors (SSRIs) are considered as a principal treatment for depression. They might exhibit a skeletal effect due to the existence of functioning serotonergic pathways in the bone evidenced by its harmful effects in the postmenopausal period. It was shown previously that leptin is involved in bone turnover regulation. Objective:The purpose of the present study was to investigate the effects of sertraline (an SSRI) on bone turnover of female rats, leptin involvement and its independence of that effect on estrogen. Method: Groups of bilaterally ovariectomized (performed 4weeks before starting treatment) & non-ovariectomized Wistar rats received sertraline (10&20mg/kg) for 4 weeks. Serum estradiols, serum osteocalcin, urinary hydroxyproline, mineral content of femur, serum leptin, and hypothalamic leptin receptor mRNA expression as well as histopathological studies were assessed. Results: The results showed sertraline increased bone turnover and decreased bone mineral content in both non-ovariectomized and ovariectomized rats. It also decreased the level of leptin peripherally as well as the hypothalamic leptin receptor mRNA expression in both OVX & NOVX groups. Conclusion: These findings suggest that SSRIs, which are frequently prescribed as antidepressants, have an undesirable impact on bone, which is probably not dependent on estrogen. Moreover, sertraline modulates leptin level centrally and peripherally, indicating its mechanistic involvement.
“…This study was done on NOVX and OVX rats in an attempt to clarify this. It is well known that ovariectomy induces weight gain (Wellberg, 2022). Similarly in the present study, bilateral ovariectomy resulted in an increase in the body weight of rats, which was not affected by the 4week administration of sertraline.…”
Background: Selective serotonin reuptake inhibitors (SSRIs) are considered as a principal treatment for depression. They might exhibit a skeletal effect due to the existence of functioning serotonergic pathways in the bone evidenced by its harmful effects in the postmenopausal period. It was shown previously that leptin is involved in bone turnover regulation. Objective:The purpose of the present study was to investigate the effects of sertraline (an SSRI) on bone turnover of female rats, leptin involvement and its independence of that effect on estrogen. Method: Groups of bilaterally ovariectomized (performed 4weeks before starting treatment) & non-ovariectomized Wistar rats received sertraline (10&20mg/kg) for 4 weeks. Serum estradiols, serum osteocalcin, urinary hydroxyproline, mineral content of femur, serum leptin, and hypothalamic leptin receptor mRNA expression as well as histopathological studies were assessed. Results: The results showed sertraline increased bone turnover and decreased bone mineral content in both non-ovariectomized and ovariectomized rats. It also decreased the level of leptin peripherally as well as the hypothalamic leptin receptor mRNA expression in both OVX & NOVX groups. Conclusion: These findings suggest that SSRIs, which are frequently prescribed as antidepressants, have an undesirable impact on bone, which is probably not dependent on estrogen. Moreover, sertraline modulates leptin level centrally and peripherally, indicating its mechanistic involvement.
“…These experiments reiterate that not all ER-positive breast tumors continue to grow after simulated endocrine therapy in the context of obesity; however, the underlying reasons for these differences are unclear. Our prior studies implicated adipose-derived FGF1 in the obesity-driven growth of ER-positive breast tumors [ 9 , 34 ]; therefore, we hypothesized that altered signaling downstream of FGF1 may influence the differential responses of tumors to estrogen deprivation in the context of obesity. Fig.…”
Background
Obesity increases breast cancer risk and breast cancer-specific mortality, particularly for people with estrogen receptor (ER)-positive tumors. Body mass index (BMI) is used to define obesity, but it may not be the best predictor of breast cancer risk or prognosis on an individual level. Adult weight gain is an independent indicator of breast cancer risk. Our previous work described a murine model of obesity, ER-positive breast cancer, and weight gain and identified fibroblast growth factor receptor (FGFR) as a potential driver of tumor progression. During adipose tissue expansion, the FGF1 ligand is produced by hypertrophic adipocytes as a stimulus to stromal preadipocytes that proliferate and differentiate to provide additional lipid storage capacity. In breast adipose tissue, FGF1 production may stimulate cancer cell proliferation and tumor progression.
Methods
We explored the effects of FGF1 on ER-positive endocrine-sensitive and resistant breast cancer and compared that to the effects of the canonical ER ligand, estradiol. We used untargeted proteomics, specific immunoblot assays, gene expression profiling, and functional metabolic assessments of breast cancer cells. The results were validated in tumors from obese mice and breast cancer datasets from women with obesity.
Results
FGF1 stimulated ER phosphorylation independently of estradiol in cells that grow in obese female mice after estrogen deprivation treatment. Phospho- and total proteomic, genomic, and functional analyses of endocrine-sensitive and resistant breast cancer cells show that FGF1 promoted a cellular phenotype characterized by glycolytic metabolism. In endocrine-sensitive but not endocrine-resistant breast cancer cells, mitochondrial metabolism was also regulated by FGF1. Comparison of gene expression profiles indicated that tumors from women with obesity shared hallmarks with endocrine-resistant breast cancer cells.
Conclusions
Collectively, our data suggest that one mechanism by which obesity and weight gain promote breast cancer progression is through estrogen-independent ER activation and cancer cell metabolic reprogramming, partly driven by FGF/FGFR. The first-line treatment for many patients with ER-positive breast cancer is inhibition of estrogen synthesis using aromatase inhibitors. In women with obesity who are experiencing weight gain, locally produced FGF1 may activate ER to promote cancer cell metabolic reprogramming and tumor progression independently of estrogen.
“…This perception may hinder timely interventions and exacerbate the impact of sleep disorders on overall well-being. To address this attitude, interventions should target misconceptions about the normalcy of sleep disorders during perimenopause 29 , 30 . Educational campaigns can incorporate narratives from individuals who have successfully managed sleep issues during this life stage, emphasizing the benefits of seeking professional guidance.…”
This cross-sectional study aimed to explore the knowledge, attitude and practice (KAP) toward sleep disorders and sleep hygiene among perimenopausal women, who were enrolled in Dezhou region of Shandong Province between July and September 2023. A total of 720 valid questionnaires were collected (mean age: 51.28 ± 4.32 years old), and 344 (47.78%) reported experiencing insomnia. The mean scores for knowledge, attitude, practice, and Dysfunctional Beliefs and Attitudes about Sleep (DBAS) were 15.73 ± 7.60 (possible range: 0–36), 29.35 ± 3.15 (possible range: 10–50), 28.54 ± 4.03 (possible range: 10–50), and 6.79 ± 1.90 (possible range: 0–10), respectively. Path analysis showed that knowledge had direct effects on attitude (β = 0.04, 95% CI 0.01–0.07, P = 0.001), and DBAS (β = 0.04, 95% CI 0.02–0.05, P < 0.001). Knowledge had direct effects (β = 0.11, 95% CI 0.08–0.15, P < 0.001) and indirect (β = 0.02, 95% CI 0.00–0.03, P = 0.002) effect on practice. Moreover, attitude also had a direct impact on practice (β = 0.34, 95% CI 0.25–0.43, P < 0.001). In conclusion, perimenopausal women exhibited insufficient knowledge, negative attitude, inactive practice toward sleep disorders and sleep hygiene, and unfavorable DBAS, emphasizing the need for targeted healthcare interventions.
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