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Peiwen Zheng School of Mental Health, Wenzhou Medical University, The Affiliated Kangning Hospital, Wenzhou, China

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Fan Wang Beijing Hui-Long-Guan Hospital, Peking University, Beijing, China

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Hui Li Psychosomatic Medicine Research Division, Inner Mongolia Medical University, Huhhot, China

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Hanlu Chen School of Mental Health, Wenzhou Medical University, The Affiliated Kangning Hospital, Wenzhou, China

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Mengtong Li School of Mental Health, Wenzhou Medical University, The Affiliated Kangning Hospital, Wenzhou, China

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Haozheng Ma School of Mental Health, Wenzhou Medical University, The Affiliated Kangning Hospital, Wenzhou, China

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Jue He School of Mental Health, Wenzhou Medical University, The Affiliated Kangning Hospital, Wenzhou, China

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Li Chen School of Mental Health, Wenzhou Medical University, The Affiliated Kangning Hospital, Wenzhou, China

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Yanlong Liu School of Mental Health, Wenzhou Medical University, The Affiliated Kangning Hospital, Wenzhou, China

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Haiyun Xu School of Mental Health, Wenzhou Medical University, The Affiliated Kangning Hospital, Wenzhou, China

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Objective

This study aimed to reveal associations between metabolic hormones in cerebral spinal fluid (CSF) and cigarette smoking-induced weight gain and to explore the underlying mechanism.

Methods

A total of 156 adult men were included, comprising active smokers and nonsmokers. In addition to demographic information and body mass index (BMI), plasma levels of ApoA1 and ApoB, high-density lipoprotein, low-density lipoprotein, cholesterol, triglyceride, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase in the participants were measured. Moreover, the metabolic hormones adiponectin, fibroblast growth factor 21 (FGF21), ghrelin, leptin, and orexin A, as well as the trace elements iron and zinc in CSF, were assessed.

Results

Compared to nonsmokers, active smokers showed higher BMI, and elevated CSF levels of FGF21, Zn, and Fe, but decreased levels of metabolic hormones adiponectin, ghrelin, leptin, and orexin A. Negative correlations existed between CSF FGF21 and ghrelin, between CSF Zn and ghrelin, as well as between CSF Fe and orexin A in active smokers. Furthermore, elevated CSF FGF21 and Zn predicted ghrelin level decrease in the smokers.

Conclusion

These data relate smoking-induced weight gain to its neurotoxic effect on the neurons that synthesize metabolic hormones such as adiponectin, ghrelin, leptin, or orexin A in the brain, by disrupting mitochondrial function and causing oxidative stress in the neurons.

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Carlijn A Hoekx Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Borja Martinez-Tellez Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
Department of Nursing Physiotherapy and Medicine, SPORT Research Group (CTS-1024), CERNEP Research Center, University of Almería, Almería, Spain
Biomedical Research Unit, Torrecárdenas University Hospital, Almería, Spain
CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Granada, Spain

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Maaike E Straat Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Magdalena M A Verkleij Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Mirjam Kemmeren Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Sander Kooijman Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Martin Uhrbom Bioscience Metabolism, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca Gothenburg, Sweden
Department of Medicine, Huddinge, Karolinska Institutet Campus Flemingsberg, Neo Building, Huddinge, Sweden

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Saskia C A de Jager Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands

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Patrick C N Rensen Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Mariëtte R Boon Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Objectives

Cold exposure is linked to cardiometabolic benefits. Cold activates brown adipose tissue (BAT), increases energy expenditure, and induces secretion of the hormones fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15). The cold-induced increase in energy expenditure exhibits a diurnal rhythm in men. Therefore, we aimed to investigate the effect of cold exposure on serum FGF21 and GDF15 levels in humans and whether cold-induced changes in FGF21 and GDF15 levels differ between morning and evening in males and females.

Method

In this randomized cross-over study, serum FGF21 and GDF15 levels were measured in healthy lean males (n = 12) and females (n = 12) before, during, and after 90 min of stable cold exposure in the morning (07:45 h) and evening (19:45 h) with a 1-day washout period in between.

Results

Cold exposure increased FGF21 levels in the evening compared to the morning both in males (+61% vs −13%; P < 0.001) and in females (+58% vs +8%; P < 0.001). In contrast, cold exposure did not significantly modify serum GDF15 levels, and no diurnal variation was found. Changes in FGF21 and GDF15 levels did not correlate with changes in cold-induced energy expenditure in the morning and evening.

Conclusion

Cold exposure increased serum FGF21 levels in the evening, but not in the morning, in both males and females. GDF15 levels were not affected by cold exposure. Thus, this study suggests that the timing of cold exposure may influence cold-induced changes in FGF21 levels but not GDF15 levels and seems to be independent of changes in energy expenditure.

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Yunting Lin Department of Surgical Medicine, Ningbo Medical Center Lihuili Hospital, Ningbo, Zhejiang, China

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Endi Song Department of Internal Medicine, Ningbo Yinzhou No.2 Hospital, Ningbo, Zhejiang, China

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Han Jin Department of Medicine, Ningbo University, Ningbo, Zhejiang, China

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Yong Jin Department of Internal Medicine, Ningbo Yinzhou No.2 Hospital, Ningbo, Zhejiang, China

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Background

Reproductive hormones may be a risk factor for cardiovascular disease (CVD), but their influence is often underestimated. Obesity can exacerbate the progression of CVD. Arterial stiffness (AS) is correlated with the risk of CVD. Brachial-ankle pulse wave velocity (baPWV) has served as a practical tool for assessing AS with broad clinical applications. This study aimed to investigate the association between reproductive hormones and baPWV in obese male and female subjects.

Methods

A retrospective case–control design was designed. AS was assessed using baPWV, with a baPWV ≥ 1400 cm/s indicating increased AS. Between September 2018 and October 2022, 241 obese subjects with increased AS were recruited from Ningbo Yinzhou No. 2 Hospital. The control group consisted of 241 obese subjects without increased AS. A 1:1 propensity score matching was performed to correct potential confounders by age and sex. We additionally performed a sex-based sub-analysis.

Results

Correlation analysis demonstrated that luteinizing hormone (LH) (r = 0.214, P = 0.001) and follicle-stimulating hormone (FSH) (r = 0.328, P < 0.001) were positively correlated with baPWV in obese male subjects. In the multivariate conditional logistic regression analysis, FSH (OR = 1.407, 95% CI = 1.040–1.902, P = 0.027) rather than LH (OR = 1.210, 95% CI = 0.908–1.612, P = 0.194) was independently and positively associated with increased AS in obese male subjects. However, there was no significant correlation between reproductive hormones and baPWV in women.

Conclusions

Our study identified FSH as a potential risk factor for arteriosclerosis in obese male subjects. This provides a novel and intriguing perspective on the pathogenesis of CVD in obese subjects.

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