Lipotoxicity suppresses the synthesis of growth hormone in pituitary somatotrophs via endoplasmic reticulum stress

Gong, Ying; Yang, Junru; Wei, Shuoshuo; Yang, Rui; Gao, Ling; Shao, Shanshan; Zhao, Jiajun

doi:10.1111/jcmm.16532

Cited by 8 publications

(5 citation statements)

References 41 publications

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“…We and others have speculated that the decreased secretion of gonadotropins observed after lipid/insulin infusion may be in part due to deleterious effects of lipid accumulation and induction of endoplasmic reticulum stress, known as lipotoxicity [ 7 , 8 , 36 , 37 ]. Since we did not observe a decrease in most other pituitary hormones and noted a transient increase in TSH, our findings argue against a non-specific pituitary lipotoxic affect and imply that gonadotroph, and perhaps somatotroph, cells are selectively targeted under conditions of hyperlipidemia and hyperinsulinemia, characteristic of obesity.…”

Section: Discussionmentioning

confidence: 99%

A randomized clinical trial demonstrating cell type specific effects of hyperlipidemia and hyperinsulinemia on pituitary function

et al. 2022

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Introduction Obesity is characterized by elevated lipids, insulin resistance and relative hypogonadotropic hypogonadism, reducing fertility and increasing risk of pregnancy complications and birth defects. We termed this phenotype ‘Reprometabolic Syndrome’ and showed that it can be recapitulated by acute infusions of lipid/insulin into healthy, normal weight, eumenorrheic women. Herein, we examined the broader impact of hyperlipidemia and euglycemic hyperinsulinemia on anterior pituitary trophic hormones and their targets. Methods Serum FSH, LH, TSH, growth hormone (GH), prolactin (PRL), thyroid hormones (free T4, total T3), cortisol, IGF-1, adiponectin, leptin and creatinine were measured in a secondary analysis of an interventional crossover study of 12 normal weight cycling women who underwent saline and heparin (control) infusion, or a euglycemic insulin infusion with heparin and Intralipid® (lipid/insulin), between days 2–5 in sequential menstrual cycles. Results In contrast to the decrease in gonadotropins, FSH and LH, infusion of lipid/insulin had no significant effects on other trophic hormones; TSH, PRL or GH. Thyroid hormones (fT4 and total T3), cortisol, IGF-1, adiponectin and creatinine also did not differ between saline or lipid/insulin infusion conditions. Leptin increased in response to lipid/insulin (p<0.02). Conclusion Acute hyperlipidemia and hyperinsulinemia exerted differential, cell type specific effects on the hypothalamic-pituitary-gonadal, adrenal and thyroid axes. Elucidation of mechanisms underlying the selective modulation of pituitary trophic hormones, in response to changes in diet and metabolism, may facilitate therapeutic intervention in obesity-related neuroendocrine and reproductive dysfunction.

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Section: Discussionmentioning

confidence: 99%

A randomized clinical trial demonstrating cell type specific effects of hyperlipidemia and hyperinsulinemia on pituitary function

et al. 2022

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“…On the other hand, GH secretion is affected by lipids. Animal models of exposure to high-fat diet showed impairment of GH synthesis and decreased circulating GH levels, likely through the activation of endoplasmic reticulum stress [14]. Other nutrients, which presumably influence the GH axis, include vitamins and microelements [15].…”

Section: Gh Axismentioning

confidence: 99%

The Effects of Nutrition on Linear Growth

et al. 2022

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Linear growth is a complex process and is considered one of the best indicators of children’s well-being and health. Genetics, epigenetics and environment (mainly stress and availability of nutrients) are the main regulators of growth. Nutrition exerts its effects on growth throughout the course of life with different, not completely understood mechanisms. Cells have a sophisticated sensing system, which allows growth processes to occur in the presence of an adequate nutrient availability. Most of the nutritional influence on growth is mediated by hormonal signals, in turn sensitive to nutritional cues. Both macro- and micro-nutrients are required for normal growth, as demonstrated by the impairment of growth occurring when their intake is insufficient. Clinical conditions characterized by abnormal nutritional status, including obesity and eating disorders, are associated with alterations of growth pattern, confirming the tight link between growth and nutrition. The precise molecular mechanisms connecting nutrition to linear growth are far from being fully understood and further studies are required. A better understanding of the interplay between nutrients and the endocrine system will allow one to develop more appropriate and effective nutritional interventions for optimizing child growth.

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“…As is well known, thyroid hormones play a crucial role in regulating energy metabolism and cellular function ( 17 ). On the other hand, it is widely believed that lipotoxicity may lead to chronic cellular dysfunction and injury, with the thyroid gland considered to be the victim ( 18 , 19 ). In a study by Araujo et al.…”

Section: Introductionmentioning

confidence: 99%

The Association Between Serum Palmitic Acid and Thyroid Function

Zhou

Zhai

et al. 2022

Front. Endocrinol.

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AimEmerging evidence indicates that palmitic acid (PA) can regulate the progression and development of many diseases. However, the studies examining the association between PA and thyroid function remain sparse. We aimed to investigate the association between serum PA (sPA) and thyroid function in the US population.MethodsIn this retrospective study, a cross-sectional analysis was performed using the data pooled from the database of the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2012. The thyroid parameters investigated were mainly free triiodothyronine (FT3), free thyroxine (FT4), total T3 (TT3), TT4, thyroglobulin (Tg), thyroid-stimulating hormone (TSH), anti-thyroglobulin antibody (TgAb), and anti-thyroperoxidase antibody (TPOAb). The central sensitivity to thyroid function was evaluated by the thyroid feedback quantile-based index (TFQI), thyrotrophin thyroxine resistance index (TT4RI), and thyrotropin index (TSHI). The FT3 to FT4 ratio (FT3/FT4) was employed to evaluate peripheral sensitivity to thyroid hormones. Multiple imputation was applied to handle the missing data, and weighted multivariable linear regression, subgroup, and interaction analyses were then employed to estimate the association between sPA and thyroid parameters.ResultsIn the 737 adults, after adjusting covariates, we demonstrated a significant negative association between sPA and FT4 [β = -1.078, 95% confidence interval (CI): -1.729 to -0.427], as well as a positive relationship between sPA and FT3/FT4 ratio (β = 0.073, 95% CI: 0.044 to 0.102). These results did not change on multiple imputations. In the subgroup analyses, the associations were more significant in male and obese subjects.ConclusionThis investigation demonstrated the significant correlation between sPA and thyroid dysfunction, which suggested the close relationship between lipotoxicity and hypothyroidism or subclinical hypothyroidism. Future research is required to confirm these findings.

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Lipotoxicity suppresses the synthesis of growth hormone in pituitary somatotrophs via endoplasmic reticulum stress

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 8 publications

References 41 publications

A randomized clinical trial demonstrating cell type specific effects of hyperlipidemia and hyperinsulinemia on pituitary function

A randomized clinical trial demonstrating cell type specific effects of hyperlipidemia and hyperinsulinemia on pituitary function

The Effects of Nutrition on Linear Growth

The Association Between Serum Palmitic Acid and Thyroid Function

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