Increased fibrosis: A novel means by which GH influences white adipose tissue function

Householder, Lara A.; Comisford, Ross; Duran‐Ortiz, Silvana; Lee, Kevin; Troike, Katie; Wilson, Christopher C.; Jara, Adam; Harberson, Mitchell; List, Edward O.; Kopchick, John J.; Berryman, Darlene E.

doi:10.1016/j.ghir.2017.12.010

Cited by 22 publications

(26 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To accomplish these goals, we used RNA-seq as an exploratory tool to elucidate the effect of increased AT of patients with acromegaly compared to controls (individuals with non-functioning pituitary adenoma), which also showed an up-regulation of genes that are induced by GH action, such as IGFBP3. 37 As might be expected based on many studies that show greater alterations in the Subq AT of bGH mice compared to other depots, 24,31,38 the bGH mice have more significant DEG in the Subq AT depot than in the Epi AT depot. These results are congruent with the well-established increase in lipolysis 18,19 and decrease in lipogenesis caused by GH on AT.…”

Section: Discussionmentioning

confidence: 65%

“…42 Although this relationship has garnered little attention in AT, the potential importance between GH function and BCAA metabolism warrants further exploration. to have more pronounced alterations in immune cell infiltration 38 and fibrosis, 24 promoting a 'pro-inflammatory' state in that depot. 24 Other studies have implicated the GH/IGF-1 axis in the modulation of the fibrotic and immune response in several tissues.…”

Section: Discussionmentioning

confidence: 99%

“…to have more pronounced alterations in immune cell infiltration 38 and fibrosis, 24 promoting a 'pro-inflammatory' state in that depot. 24 Other studies have implicated the GH/IGF-1 axis in the modulation of the fibrotic and immune response in several tissues.…”

Section: Discussionmentioning

confidence: 99%

“…18,19 However, the impact of GH on AT extends beyond its role in the lipogenic/lipolytic processes. 20 GH also influences preadipocyte differentiation and proliferation, 21 preadipocyte senescence, 22 fibrosis, 23,24 beiging, 2 adipokine secretion 20 and immune cell abundance. 25 Furthermore, in vivo, GH has been shown to influence AT in a depot-specific manner because subcutaneous (Subq) and intraabdominal AT tissues respond differently and with varying intensities to GH action.…”

Section: Introductionmentioning

confidence: 99%

“…28 As for bGH mice, AT mass is reduced, which becomes more prominent with advancing age and in male mice. 7 bGH mice also have (i) altered adipokine production with reduced leptin and adiponectin [29][30][31] ; (ii) altered hormone sensitivity with reduced insulin-like growth factor (IGF)-1 receptor and GHR expression levels 32 ; (iii) increased extracellular matrix deposition (most prominently in Subq) 24 ; (iv) increased beiging markers in Subq depots 33 ; (v) impaired preadipocyte differentiation of mesenchymal stem cells in Subq 25 ; (vi) increased senescent cell burden of preadipocytes in all depots except perigonadal (epididymal) 22 ; and (vii) AT immune cell infiltration with greater macrophage and regulatory T-cell infiltration of only Subq depots. 25 Even though GH is well known to impact AT metabolism and plasticity, the molecular mechanisms and pathways responsible for the depot-specific effects of GH are still largely unknown.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Differential gene signature in adipose tissue depots of growth hormone transgenic mice

Duran‐Ortiz

Young

Jara

et al. 2020

J Neuroendocrinology

Self Cite

View full text Add to dashboard Cite

Bovine growth hormone (bGH) transgenic mice mimic the clinical condition of acromegaly, having high circulating growth hormone (GH) levels. These mice are giant, have decreased adipose tissue (AT) mass, impaired glucose metabolism and a shortened lifespan. The detrimental effects of excess GH have been suggested, in part, to be a result of its depot-specific actions on AT. To investigate this relationship, we evaluated gene expression, biological mechanisms, cellular pathways and predicted microRNA (miRNA) in two AT depots (subcutaneous [Subq] and epididymal [Epi]) from bGH and littermate controls using RNA sequencing analysis. Two analyses on the differentially expressed genes (DEG) were performed: (i) comparison of the same AT depot between bGH and wild-type (WT) mice (genotype comparison) and (ii) comparison of Subq and Epi AT depots within the same genotype (depot comparison). For the genotype comparison, we found a higher number of significant DEG in the Subq AT depot of bGH mice compared to WT controls, corroborating previous reports that GH has a greater impact on the Subq depot. Furthermore, most of the DEG in bGH mice were not shared by WT mice, suggesting that excess GH induces the expression of genes not commonly present in AT. Through gene ontology and pathway analysis, the genotype comparison revealed that the DEG of the Subq depot of bGH mice relate to fatty acid oxidation, branched-chain amino acid degradation and the immune system. Additionally, the AT depot comparison showed that the immune cell activation and T-cell response appear up-regulated in the Subq compared to the Epi AT depot. The miRNA prediction also suggested a modulation of T-cell-related biological process in Subq. In summary, the present study provides a unique resource for understanding the specific differences in gene expression that are driven by both excess GH action and AT depot location.

show abstract

Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Differential gene signature in adipose tissue depots of growth hormone transgenic mice

Duran‐Ortiz

Young

Jara

et al. 2020

J Neuroendocrinology

Self Cite

View full text Add to dashboard Cite

show abstract

Transcriptome profiling of insulin sensitive tissues from GH deficient mice following GH treatment

et al. 2021

View full text Add to dashboard Cite

Growth hormone alters gross anatomy and morphology of the small and large intestines in age- and sex-dependent manners

et al. 2021

Self Cite

View full text Add to dashboard Cite

Purpose Growth hormone (GH) has an important role in intestinal barrier function, and abnormalities in GH action have been associated with intestinal complications. Yet, the impact of altered GH on intestinal gross anatomy and morphology remains unclear. Methods This study investigated the influence of GH signaling on gross anatomy, morphology, and fibrosis by characterizing the small and large intestines in male and female bovine growth hormone transgenic (bGH) mice and GH receptor gene-disrupted (GHR−/−) mice at multiple timepoints. ResultsThe length, weight, and circumference of the small and large intestines were increased in bGH mice and decreased in GHR−/− mice across all ages. Colon circumference was significantly increased in bGH mice in a sex-dependent manner while significantly decreased in male GHR−/− mice. Villus height, crypt depth, and muscle thickness of the small intestine were generally increased in bGH mice and decreased in GHR−/− mice compared to controls with age-and sex-dependent exceptions. Colonic crypt depth and muscle thickness in bGH and GHR−/− mice were significantly altered in an age-and sex-dependent manner. Fibrosis was increased in the small intestine of bGH males at 4 months of age, but no significant differences were seen between genotypes at other timepoints. Conclusion This study observed notable opposing findings in the intestinal phenotype between mouse lines with GH action positively associated with intestinal gross anatomy (i.e. length, weight, and circumference). Moreover, GH action appears to alter morphology of the small and large intestines in an age-and sex-dependent manner.

show abstract

Increased fibrosis: A novel means by which GH influences white adipose tissue function

Cited by 22 publications

References 57 publications

Differential gene signature in adipose tissue depots of growth hormone transgenic mice

Differential gene signature in adipose tissue depots of growth hormone transgenic mice

Transcriptome profiling of insulin sensitive tissues from GH deficient mice following GH treatment

Growth hormone alters gross anatomy and morphology of the small and large intestines in age- and sex-dependent manners

Contact Info

Product

Resources

About