Browsing by Author "Zhao, Lidan"
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- Association of growth hormone deficiency with an increased number of preadipocytes in subcutaneous fatZhao, Lidan; Jia, Dan; Tan, Zhendong; Jiang, Honglin (Frontiers, 2023-05)The inhibitory effect of growth hormone (GH) on adipose tissue growth is well known, but the underlying mechanism is not fully understood. In this study, we determined the possibility that GH inhibits adipose tissue growth by inhibiting adipogenesis, the process of formation of adipocytes from stem cells, in the lit/lit mice. The lit/lit mice are GH deficient because of a spontaneous mutation to the GH releasing hormone receptor (ghrhr) gene, and they have more subcutaneous fat despite being smaller than the lit/+ mice at the same age. We found that cells of the stromal vascular fraction (SVF) of subcutaneous fat from the lit/lit mice had greater adipogenic potential than those from the lit/+ mice, as evidenced by forming greater numbers of lipid droplets-containing adipocytes and having greater expression of adipocyte marker genes during induced adipocyte differentiation in culture. However, addition of GH to the culture did not reverse the superior adipogenic potential of subcutaneous SVF from the lit/lit mice. Through florescence-activated cell sorting and quantification of mRNAs of preadipocyte markers, including CD34, CD29, Sca-1, CD24, Pref-1, and PPAR gamma, we found that subcutaneous SVF from the lit/lit mice contained more preadipocytes than that from the lit/+ mice. These results support the notion that GH inhibits adipose tissue growth in mice at least in part by inhibiting adipogenesis. Furthermore, these results suggest that GH inhibits adipogenesis in mice not by inhibiting the terminal differentiation of preadipocytes into adipocytes, rather by inhibiting the formation of preadipocytes from stem cells or the recruitment of stem cells to the fat depot.
- Diminished satellite cell fusion and S6K1 expression in myotubes derived from skeletal muscle of low birth weight neonatal pigsChen, Ying; Zhu, Haibo; McCauley, Sydney R.; Zhao, Lidan; Johnson, Sally E.; Rhoads, Robert P.; El-Kadi, Samer Wassim (The American Physiological Society, 2017-02-09)Low birth weight (LBWT) is consistently associated with impaired postnatal muscle growth in mammals. Satellite cell (SC)‐mediated myonuclear incorporation precedes protein accumulation in the early stages of postnatal muscle development and growth. The objective of this study was to investigate proliferation and differentiation of SCs and the regulation of protein synthesis signaling in response to insulin‐like growth factor (IGF)‐I stimulation in SC‐derived myotubes of LBWT neonatal pigs. SCs isolated from Longissimus dorsi muscle of LBWT and NBWT pigs (3‐d‐old, n = 8) were cultured and induced to proliferate and differentiate to myotubes in vitro. On day 3 of differentiation, myotubes were fasted in serum‐free media for 3 h and treated with human recombinant R³‐insulin‐like growth factor‐I (rh IGF‐I) at 0, 25, and 50 ng × mL⁻¹ for 30 min. There was no difference in proliferation rates of SCs from LBWT and NBWT pigs. However, LBWT SC fusion was 15% lower (P ≤ 0.05) without a difference in MyoD or myogenin mRNA expression in comparison with NBWT pigs, suggesting SCs are not intrinsically different between the two groups. IGF‐Ι stimulation at physiological concentrations activated downstream effectors of mTOR similarly in myotubes from LBWT and NBWT pigs. However, abundance of ribosomal protein S6 kinase 1(S6K1) was lower in myotubes of LBWT compared to their NBWT siblings (P ≤ 0.05). These results indicate that the modest reduction in SC fusion and S6K1 expression are not the major contributors to the impaired postnatal muscle growth of LBWT pigs.
- Growth hormone stimulates lipolysis in mice but not in adipose tissue or adipocyte cultureZhao, Lidan; Jiang, Honglin (Frontiers, 2023-01-04)The inhibitory effect of growth hormone (GH) on adipose tissue growth and the stimulatory effect of GH on lipolysis are well known, but the mechanisms underlying these effects are not completely understood. In this study, we revisited the effects of GH on adipose tissue growth and lipolysis in the lit/lit mouse model. The lit/lit mice are GH deficient because of a mutation in the GH releasing hormone receptor gene. We found that the lit/lit mice had more subcutaneous fat and larger adipocytes than their heterozygous lit/+ littermates and that these differences were partially reversed by 4-week GH injection. We also found that GH injection to the lit/lit mice caused the mature adipose tissue and adipocytes to reduce in size. These results demonstrate that GH inhibits adipose tissue growth at least in part by stimulating lipolysis. To determine the mechanism by which GH stimulates lipolysis, we cultured adipose tissue explants and adipocytes derived from lit/lit mice with GH and/or isoproterenol, an agonist of the beta-adrenergic receptors. These experiments showed that whereas isoproterenol, expectedly, stimulated potent lipolysis, GH, surprisingly, had no effect on basal lipolysis or isoproterenol-induced lipolysis in adipose tissue explants or adipocytes. We also found that both isoproterenol-induced lipolysis and phosphorylation of hormone-sensitive lipase were not different between lit/lit and lit/+ mice. Taken together, these results support the conclusion that GH has lipolytic effect in mice but argue against the notion that GH stimulates lipolysis by directly acting on adipocytes or by enhancing beta-adrenergic receptors-mediated lipolysis.
- Growth Hormone Stimulates Transcription of the Fibroblast Growth Factor 21 Gene in the Liver through the Signal Transducer and Activator of Transcription 5Yu, Jie; Zhao, Lidan; Wang, Aihua; Eleswarapu, Satyanarayana; Ge, Xiaomei; Chen, Daiwen; Jiang, Honglin (Endocrine Society, 2012-02)Fibroblast growth factor 21 (FGF21) is a recently discovered metabolic regulator. Interestingly, FGF21 is also known to inhibit Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5 (STAT5) signaling from the GH receptor in the liver, where FGF21 mRNA is predominantly expressed. In this study, we tested the hypothesis that FGF21 gene expression in the liver is controlled by GH through STAT5. We found that GH injection to cattle increased FGF21 mRNA expression in the liver. Mapped by a 5'-rapid amplification of cDNA ends assay, transcription of the FGF21 gene in the bovine liver was mainly initiated from a nucleotide 24 bp downstream of a TATA box. The bovine FGF21 promoter contains three putative STAT5-binding sites. EMSA confirmed the ability of them to bind to liver STAT5 protein from GH-injected cattle. Chromatin immunoprecipitation assays demonstrated that GH administration increased the binding of STAT5 to the FGF21 promoter in the liver. Cotransfection analyses showed that GH induced reporter gene expression from the FGF21 promoter in a STAT5-dependent manner. GH also stimulated FGF21 mRNA expression in cultured mouse hepatocytes. These data together indicate that GH directly stimulates FGF21 gene transcription in the liver, at least in part, through STAT5. This finding, together with the fact that FGF21 inhibits GH-induced JAK2-STAT5 signaling in the liver, suggests a novel negative feedback loop that prevents excessive JAK2-STAT5 signaling from the GH receptor in the liver. (Endocrinology 153: 750-758, 2012)
- Mechanisms of growth hormone inhibition of adipose tissue growthZhao, Lidan (Virginia Tech, 2013-01-14)Growth hormone (GH) is a poly-peptide hormone produced by the anterior pituitary. Growth hormone not only stimulates body and muscle growth but also inhibits adipose tissue growth. The overall objective of this study was to determine the mechanisms by which GH inhibits adipose tissue growth. Three studies were conducted to achieve this objective. The first study was conducted to determine if GH inhibits fat tissue growth by stimulating lipolysis. In this study, adipose tissue weight and adipocyte size were compared between GH-deficient growth hormone releasing hormone receptor (Ghrhr) homozygous mutant mice (i.e., lit/lit mice), lit/+ mice, and lit/lit mice injected with GH. lit/lit mice had less body weight but more subcutaneous fat and larger adipocytes compared to lit/+ mice at the same ages. GH treatment to lit/lit mice for four weeks partially reversed these differences. These data suggest that GH inhibits adipose tissue growth in mice at least in part by stimulating lipolysis. Additional data from this study suggest that GH indirectly stimulates lipolysis in vivo and this indirect mechanism is independent of " adrenergic receptors in the adipose tissue. The second study was conducted to investigate if GH inhibits fat tissue growth also by inhibiting adipogenesis. In this study, stromal vascular fraction (SVF) cells were isolated from subcutaneous fat of lit/+ and lit/lit mice and were induced to differentiate into adipocytes in vitro. Oil Red O staining and gene expression analysis revealed that the SVF cells from lit/lit mice had greater adipogenic potential than from lit/+ mice. This suggests that GH inhibits adipose tissue growth also through inhibition of adipogenesis. Additional data from this study suggest that GH may inhibit adipogenesis by inhibiting the formation of adipogenic precursor cells in adipose tissue in mice. The third study was conducted to determine the role of the central component of GH receptor signaling, STAT5, in GH inhibition of differentiation of bovine preadipocytes. In this study, preadipocytes were isolated from subcutaneous fat of adult cattle and were induced to differentiate with or without GH. Based on Oil Red O staining, gene expression, glycerol-3-phosphate dehydrogenase (G3PDH) activity and acetate incorporation assays, GH inhibited differentiation of bovine preadipocytes into adipocytes. GH induced phosphorylation of STAT5 in differentiating bovine preadipocytes. Overexpression of constitutively active STAT5 through adenovirus mimicked the effect of GH on differentiation of bovine preadipocytes. These data support a role of STAT5 in mediating the inhibitory effect of GH on differentiation of bovine preadipocytes into adipocytes. Overall, GH inhibits adipose tissue by both stimulating lipolysis and inhibiting adipogenesis; GH stimulates lipolysis through an indirect mechanism that is independent of the " adrenergic receptors; GH inhibits adipogenesis through a direct mechanism that may involve the transcription factor STAT5.
- Regulation of fibroblast growth factor 15/19 and 21 on metabolism: in the fed or fasted stateGuan, Dandan; Zhao, Lidan; Chen, Daiwen; Yu, Bing; Yu, Jie (2016-03-01)Fibroblast growth factor (FGF) 15/19 and FGF21 are two atypical members of FGF19 subfamily that function as hormones. Exogenous FGF15/19 and FGF21 have pharmacological effects, and endogenous FGF15/19 and FGF21 play vital roles in the maintenance of energy homeostasis. Recent reports have expanded the effects of FGF15/19 and FGF21 on carbohydrate and lipid metabolism. However, the regulations of FGF15/19 and FGF21 on metabolism are different. FGF15/19 is mainly secreted from the small intestine in response to feeding, and FGF21 is secreted from the liver in response to extended fasting and from the liver and adipose tissue in response to feeding. In this work, we reviewed the regulatory effects of FGF15/19 and FGF21 on metabolism in the fast and fed states. This information may provide some insight into the metabolic regulation of FGF15/19 and FGF21 in different physiological condition.