Association between Serum Growth Hormone Levels and Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study

Xu, Lei; Xu, Chengfu; Yu, Chaohui; Miao, Min; Zhang, Xuequn; Zhu, Zhongwei; Ding, Xiaoyun; Li, Youming

doi:10.1371/journal.pone.0044136

Cited by 64 publications

(48 citation statements)

References 29 publications

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“…In a large cross-sectional study including 1667 patients diagnosed with NAFLD and 5479 controls, random GH levels were lower in the NAFLD group (0.02 vs 0.11 ng/ml) (56). GH levels were negatively correlated with other features of the metabolic syndrome and the NAFLD cohort was significantly older.…”

Section: Oestrogensmentioning

confidence: 93%

Mechanisms in endocrinology: Non-alcoholic fatty liver disease in common endocrine disorders

Hazlehurst

Tomlinson

2013

European Journal of Endocrinology

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Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease spanning from simple benign steatosis to steatohepatitis with fibrosis and scarring that can eventually lead to cirrhosis. Its prevalence is rising rapidly and is developing into the leading indication for liver transplantation worldwide. Abnormalities in endocrine axes have been associated with NALFD, including hypogonadism, hypothyroidism, GH deficiency and hypercortisolaemia. In some instances, correction of the endocrine defects has been shown to have a beneficial impact. While in patients with type 2 diabetes the association with NAFLD is well established and recognised, there is a more limited appreciation of the condition among common endocrine diseases presenting with hormonal excess or deficiency. In this review, we examine the published data that have suggested a mechanistic link between endocrine abnormalities and NAFLD and summarise the clinical data endorsing these observations.

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Section: Oestrogensmentioning

confidence: 93%

Mechanisms in endocrinology: Non-alcoholic fatty liver disease in common endocrine disorders

Hazlehurst

Tomlinson

2013

European Journal of Endocrinology

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“…In one cohort of growth hormone-deficient patients, 77% presented with NAFLD (Nishizawa et al 2012). Conversely, individuals with NAFLD were found to have significantly lower growth hormone levels than controls (Xu et al 2012). Cushing's syndrome is present in 0.00025% of the general population, yet exists in 1.4% of type 2 diabetics with 3.4% displaying hypercortisolemia (Steffensen et al 2016).…”

Section: Introductionmentioning

confidence: 97%

Hepatic lipid accumulation: cause and consequence of dysregulated glucoregulatory hormones

Geisler

Renquist

2017

Journal of Endocrinology

156

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Fatty liver can be diet, endocrine, drug, virus or genetically induced. Independent of cause, hepatic lipid accumulation promotes systemic metabolic dysfunction. By acting as peroxisome proliferator-activated receptor (PPAR) ligands, hepatic non-esterified fatty acids upregulate expression of gluconeogenic, beta-oxidative, lipogenic and ketogenic genes, promoting hyperglycemia, hyperlipidemia and ketosis. The typical hormonal environment in fatty liver disease consists of hyperinsulinemia, hyperglucagonemia, hypercortisolemia, growth hormone deficiency and elevated sympathetic tone. These endocrine and metabolic changes further encourage hepatic steatosis by regulating adipose tissue lipolysis, liver lipid uptake, de novo lipogenesis (DNL), beta-oxidation, ketogenesis and lipid export. Hepatic lipid accumulation may be induced by 4 separate mechanisms: (1) increased hepatic uptake of circulating fatty acids, (2) increased hepatic de novo fatty acid synthesis, (3) decreased hepatic beta-oxidation and (4) decreased hepatic lipid export. This review will discuss the hormonal regulation of each mechanism comparing multiple physiological models of hepatic lipid accumulation. Nonalcoholic fatty liver disease (NAFLD) is typified by increased hepatic lipid uptake, synthesis, oxidation and export. Chronic hepatic lipid signaling through PPARgamma results in gene expression changes that allow concurrent activity of DNL and beta-oxidation. The importance of hepatic steatosis in driving systemic metabolic dysfunction is highlighted by the common endocrine and metabolic disturbances across many conditions that result in fatty liver. Understanding the mechanisms underlying the metabolic dysfunction that develops as a consequence of hepatic lipid accumulation is critical to identifying points of intervention in this increasingly prevalent disease state.

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“…Low levels of growth hormone (GH) in the general population associate with NAFLD (2). Multi–single nucleotide polymorphism analyses of genome-wide association study have revealed 18 single nucleotide polymorphisms in the GH pathway that relate to the development and progression of NAFLD (3).…”

Section: Introductionmentioning

confidence: 99%

“…Also, patients with GH receptor (GHR) loss of function (Laron syndrome) exhibit NAFLD (4). Likewise, cessation of GH treatment in GH-deficient (GHD) children after achieving adult height leads to development of NAFLD and dyslipidemia in 29% of patients surveyed 10 years after therapy (2). Importantly, reductions in circulating GH (2,5) or its mediator, IGF-1 (6–8), associate with NAFLD even after adjusting to BMI (9).…”

Section: Introductionmentioning

confidence: 99%

“…Likewise, cessation of GH treatment in GH-deficient (GHD) children after achieving adult height leads to development of NAFLD and dyslipidemia in 29% of patients surveyed 10 years after therapy (2). Importantly, reductions in circulating GH (2,5) or its mediator, IGF-1 (6–8), associate with NAFLD even after adjusting to BMI (9). Obese patients manifest GH resistance and can show declines in GH (10,11) that may be as low as those observed in GHD subjects (12,13).…”

Section: Introductionmentioning

confidence: 99%

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Growth Hormone Control of Hepatic Lipid Metabolism

et al. 2016

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In humans, low levels of growth hormone (GH) and its mediator, IGF-1, associate with hepatic lipid accumulation. In mice, congenital liver-specific ablation of the GH receptor (GHR) results in reductions in circulating IGF-1 and hepatic steatosis, associated with systemic insulin resistance. Due to the intricate relationship between GH and IGF-1, the relative contribution of each hormone to the development of hepatic steatosis is unclear. Our goal was to dissect the mechanisms by which hepatic GH resistance leads to steatosis and overall insulin resistance, independent of IGF-1. We have generated a combined mouse model with liver-specific ablation of GHR in which we restored liver IGF-1 expression via the hepatic IGF-1 transgene. We found that liver GHR ablation leads to increases in lipid uptake, de novo lipogenesis, hyperinsulinemia, and hyperglycemia accompanied with severe insulin resistance and increased body adiposity and serum lipids. Restoration of IGF-1 improved overall insulin sensitivity and lipid profile in serum and reduced body adiposity, but was insufficient to protect against steatosis-induced hepatic inflammation or oxidative stress. We conclude that the impaired metabolism in states of GH resistance results from direct actions of GH on lipid uptake and de novo lipogenesis, whereas its actions on extrahepatic tissues are mediated by IGF-1.

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Association between Serum Growth Hormone Levels and Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study

Cited by 64 publications

References 29 publications

Mechanisms in endocrinology: Non-alcoholic fatty liver disease in common endocrine disorders

Mechanisms in endocrinology: Non-alcoholic fatty liver disease in common endocrine disorders

Hepatic lipid accumulation: cause and consequence of dysregulated glucoregulatory hormones

Growth Hormone Control of Hepatic Lipid Metabolism

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