The effects of growth hormone on adipose tissue: old observations, new mechanisms

Kopchick, John J.; Berryman, Darlene E.; Puri, Vishwajeet; Lee, Kevin Y.; Jørgensen, Jens Otto Lunde

doi:10.1038/s41574-019-0280-9

Cited by 118 publications

(91 citation statements)

References 160 publications

(183 reference statements)

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“…The changes in AT mass we observed with GHR antagonist therapy are consistent with reversal of the mechanisms by which GH reduces AT, in particular VAT, mass [ 36-41 ]. The effects of pegvisomant on fat metabolism have been studied in a few prior, short-term studies in acromegaly and healthy subjects and showed no changes [ 31 , 42 , 43 ] or suppression of lipid mobilization and oxidation [ 44 ].…”

Section: Discussionsupporting

confidence: 67%

Body Composition Changes with Long-term Pegvisomant Therapy of Acromegaly

Shen

Jin

Singh

et al. 2021

Journal of the Endocrine Society

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Context In active acromegaly, the lipolytic and insulin antagonistic effects of growth hormone (GH) excess alter adipose tissue (AT) deposition, reduce body fat, and increase insulin resistance. This pattern reverses with surgical therapy. Pegvisomant treats acromegaly by blocking GH receptor (GHR) signal transduction and lowering insulin-like growth factor 1 (IGF-1) levels. The long-term effects of GHR antagonist treatment of acromegaly on body composition have not been studied. Methods We prospectively studied 21 patients with active acromegaly who were starting pegvisomant. Body composition was examined by whole body magnetic resonance imaging, proton magnetic resonance spectroscopy of liver and muscle and dual-energy x-ray absorptiometry, and endocrine and metabolic markers were measured before and serially during 1.0 to 13.4 years of pegvisomant therapy. The data of patients with acromegaly were compared with predicted and to matched controls. Results Mass of visceral AT (VAT) increased to a peak of 187% (1.56-229%) (P < .001) and subcutaneous AT (SAT) to 109% (–17% to 57%) (P = .04) of baseline. These remained persistently and stably increased, but did not differ from predicted during long-term pegvisomant therapy. Intrahepatic lipid rose from 1.75% to 3.04 % (P = .04). Although lean tissue mass decreased significantly, skeletal muscle (SM) did not change. IGF-1 levels normalized, and homeostasis model assessment insulin resistance and HbA1C were lowered. Conclusion Long-term pegvisomant therapy is accompanied by increases in VAT and SAT mass that do not differ from predicted, stable SM mass and improvements in glucose metabolism. Long-term pegvisomant therapy does not produce a GH deficiency-like pattern of body composition change.

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Section: Discussionsupporting

confidence: 67%

Body Composition Changes with Long-term Pegvisomant Therapy of Acromegaly

Shen

Jin

Singh

et al. 2021

Journal of the Endocrine Society

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“…The recuperation of the GH–IGF-1 axis after body weight normalization suggests an acquired and reversible disturbance; however, the reduced GH secretion in obesity may favor the retention of adipose tissue, and contribute to perpetuation of the obese state. GH’s most characteristic metabolic action is to induce adipose tissue lipolysis [ 49 ]. GH directly stimulates adipose tissue lipolysis in a GH receptor-dependent manner [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Altered GH-IGF-1 Axis in Severe Obese Subjects is Reversed after Bariatric Surgery-Induced Weight Loss and Related with Low-Grade Chronic Inflammation

Juiz-Valiña

Pena-Bello

Cordido

et al. 2020

JCM

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Endocrine disorders are common in obesity, including altered somatotropic axis. Obesity is characterized by reduced growth hormone (GH) secretion, although the insulin-like growth factor-1 (IGF-1) values are controversial. The aim of this study was to evaluate the effect of weight loss after bariatric surgery in the GH–IGF-1 axis in extreme obesity, in order to investigate IGF-1 values and the mechanism responsible for the alteration of the GH–IGF-1 axis in obesity. We performed an interventional trial in morbidly obese patients who underwent bariatric surgery. We included 116 patients (97 women) and 41 controls (30 women). The primary endpoint was circulating GH and IGF-1 values. Circulating IGF-1 values were lower in the obese patients than in the controls. Circulating GH and IGF-1 values increased significantly over time after surgery. Post-surgery changes in IGF-1 and GH values were significantly negatively correlated with changes in C-reactive protein (CRP) and free T4 values. After adjusting for preoperative body mass index (BMI), free T4 and CRP in a multivariate model, only CRP was independently associated with IGF-1 values in the follow-up. In summary, severe obesity is characterized by a functional hyposomatotropism at central and peripheral level that is progressively reversible with weight loss, and low-grade chronic inflammation could be the principal mediator.

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“…GH is widely recognized for its anabolic and lipolytic functions, stimulating muscle and bone growth mediated by IGF1 secretion. In adipocytes, stimulated GH receptors induce lipolysis through oxidation and triacylglycerol breakdown [86]. On the other hand, the homeobox transcript antisense intergenic RNA (HOTAIR) is part of the long noncoding RNAs class that is suggested to regulate the expression of numerous signalling transcripts and is a potential biomarker for several types of cancer [87].…”

Section: Functional Analysismentioning

confidence: 99%

Comparative Transcriptomic Analysis of Subcutaneous Adipose Tissue from Local Pig Breeds

Albuquerque

Óvilo

Núñez

et al. 2020

Genes

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When compared to modern lean-type breeds, Portuguese local Alentejano (AL) and Bísaro (BI) pig breeds present a high potential for subcutaneous and intramuscular fat (IMF) deposition which contributes for better meat quality. The aim of this work was to explore the genome function to better understand the underlying physiological mechanisms associated with body fat accretion. Dorsal subcutaneous fat samples were collected at slaughter from adult animals (n = 4 for each breed) with~150 kg body weight. Total RNA was obtained and sequenced for transcriptome analysis using DESeq2. A total of 458 differentially expressed (DE) genes (q-value < 0.05) were identified, with 263 overexpressed in AL and 195 in BI. Key genes involved in de novo fatty acid biosynthesis, elongation and desaturation were upregulated in AL such as ACLY, FASN, ME1, ELOVL6 and SCD. A functional enrichment analysis of the DE genes was performed using Ingenuity Pathway Analysis. Cholesterol synthesis is suggested to be higher in AL via SREBF2, SCAP and PPARG, while lipolytic activity may be more active in BI through GH and AMPK signalling. Increased signalling of CD40 together with the predicted activation of INSIG1 and INSIG2 in BI suggests that this breed is more sensitive to insulin whereas the AL is less sensitive like the Iberian breed.Genes 2020, 11, 422 2 of 20 inherent genetic value for biodiversity, local breeds are used to produce high quality dry-cured meat products, representing an important role in local economies, culture and landscape as the basics of sustainable local pork chains [2,4].Alentejano (AL) and Bísaro (BI) are the two main Portuguese pig breeds. AL evolved from the primitive Sus scrofa mediterraneus, belongs to the Mediterranean group of breeds [5] and is genetically similar to the Iberian (IB) pig [6]. This breed is commonly raised in the south of Portugal and generally characterized by its light bone structure, black color, short and slim extremities and energetic nature [7]. A medium-sized pig, the AL grows at a low rate (except under the finishing phase "montanheira") and presents a low prolificacy [8]. On the other hand, its high and early adipogenic activity provides a meat and fat composition that is attractive for both fresh meat market and for processing high-grade sausage and dry cured products [9,10]. Traditionally, the AL pig is raised under extensive conditions in an integrated pastoral system ("montado") and during the fattening season is fed with acorns from the existing Quercus forests from October to February [5,7]. BI breed belongs to the Celtic group [5], sharing ancestors with highly productive breeds such as Large-White and Landrace. Production of BI is distributed throughout the north of Portugal, from the Tagus River to the northern border with Spain. It is characterized by its docile temperament, presenting a large body with large legs, head and shoulders. BI pig presents a higher prolificacy and productivity than AL, though lower than other genotypes with similar origins but raised under intensive ...

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The effects of growth hormone on adipose tissue: old observations, new mechanisms

Cited by 118 publications

References 160 publications

Body Composition Changes with Long-term Pegvisomant Therapy of Acromegaly

Body Composition Changes with Long-term Pegvisomant Therapy of Acromegaly

Altered GH-IGF-1 Axis in Severe Obese Subjects is Reversed after Bariatric Surgery-Induced Weight Loss and Related with Low-Grade Chronic Inflammation

Comparative Transcriptomic Analysis of Subcutaneous Adipose Tissue from Local Pig Breeds

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