Leptin and regulation of linear growth

Gat-Yablonski, Galia; Phillip, Moshe

doi:10.1097/mco.0b013e3282f795cf

Cited by 79 publications

(52 citation statements)

References 53 publications

(54 reference statements)

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“…Leptin enhances growth hormone-releasing hormone (GHRH)-induced GH secretion in rat anterior pituitary cells in vitro (216). Furthermore, it has been shown that leptin blunts the fasting-induced decrease in GH and increases longitudinal bone growth in normal rodents (81).…”

Section: Physiological Role Of Leptin In the Regulation Of Neuroendocmentioning

confidence: 99%

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Leptin in human physiology and pathophysiology

Mantzoros

Magkos

Brinkoetter

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

482

306

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Leptin, discovered through positional cloning 15 years ago, is an adipocyte-secreted hormone with pleiotropic effects in the physiology and pathophysiology of energy homeostasis, endocrinology, and metabolism. Studies in vitro and in animal models highlight the potential for leptin to regulate a number of physiological functions. Available evidence from human studies indicates that leptin has a mainly permissive role, with leptin administration being effective in states of leptin deficiency, less effective in states of leptin adequacy, and largely ineffective in states of leptin excess. Results from interventional studies in humans demonstrate that leptin administration in subjects with congenital complete leptin deficiency or subjects with partial leptin deficiency (subjects with lipoatrophy, congenital or related to HIV infection, and women with hypothalamic amenorrhea) reverses the energy homeostasis and neuroendocrine and metabolic abnormalities associated with these conditions. More specifically, in women with hypothalamic amenorrhea, leptin helps restore abnormalities in hypothalamic-pituitary-peripheral axes including the gonadal, thyroid, growth hormone, and to a lesser extent adrenal axes. Furthermore, leptin results in resumption of menses in the majority of these subjects and, in the long term, may increase bone mineral content and density, especially at the lumbar spine. In patients with congenital or HIVrelated lipoatrophy, leptin treatment is also associated with improvements in insulin sensitivity and lipid profile, concomitant with reduced visceral and ectopic fat deposition. In contrast, leptin's effects are largely absent in the obese hyperleptinemic state, probably due to leptin resistance or tolerance. Hence, another emerging area of research pertains to the discovery and/or usefulness of leptin sensitizers. Results from ongoing studies are expected to further increase our understanding of the role of leptin and the potential clinical applications of leptin or its analogs in human therapeutics. adipokines; adipose tissue; leptin resistance; leptin deficiency; hypoleptinemia STUDIES OF GENETICALLY OBESE MICE serendipitously found in the Jackson Laboratories revealed that their phenotypes derive from homozygous mutations of either the obese (ob) or diabetic (db) genes that result in obesity and insulin resistance or diabetes as well as endocrine and immune dysfunction (53, 54,115,117,183,261). The gene mutation in the ob/ob mouse results in a complete deficiency of or a truncated and biologically inactive ob gene product (287); the latter subsequently was given the name leptin (95), from the Greek word "leptos" (meaning "thin"), because when this protein was given to the obese ob/ob mice they lost significant amounts of body weight. It was then recognized that the db gene codes for the leptin receptor (140). Consequently, exogenously administered leptin reduces body weight and resolves the metabolic, endocrine, and immune disturbances in ob/ob mice but has no effects in db/db mice (100, 111, 28...

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Section: Physiological Role Of Leptin In the Regulation Of Neuroendocmentioning

confidence: 99%

“…Both ob/ob and db/db mice have stunted growth curves and fragile growth plates (80,81). Leptin enhances growth hormone-releasing hormone (GHRH)-induced GH secretion in rat anterior pituitary cells in vitro (216).…”

Section: Physiological Role Of Leptin In the Regulation Of Neuroendocmentioning

confidence: 99%

Leptin in human physiology and pathophysiology

Mantzoros

Magkos

Brinkoetter

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

482

306

View full text Add to dashboard Cite

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“…The direct actions of leptin are through the leptin receptor (OBR (LEPR)), which is present in the growth plate (Nakajima et al 2003, Kishida et al 2005. Activation of OBR by leptin leads to the activation of many signaling pathways including the JAK1/STAT1 pathway and the phosphatidylinositol 3-kinase (PI3K (PIK3R1))/MAPK1 pathway, both of which can mediate the differentiation of chondrocytes (Fruhbeck 2006, Ben-Eliezer et al 2007, Gat-Yablonski & Phillip 2008.…”

Section: Introductionmentioning

confidence: 99%

Estrogen stimulates leptin receptor expression in ATDC5 cells via the estrogen receptor and extracellular signal-regulated kinase pathways

Wang

Li²,

Jiang³

et al. 2012

Journal of Endocrinology

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Regulation of the physiological processes of endochondral bone formation during long bone growth is controlled by various factors including the hormones estrogen and leptin. The effects of estrogen are mediated not only through the direct activity of estrogen receptors (ERs) but also through cross talk with other signaling systems implicated in chondrogenesis. The receptors of both estrogen and leptin (OBR (LEPR)) are detectable in growth plate chondrocytes of all zones. In this study, the expression of mRNA and protein of OBR in chondrogenic ATDC5 cells and the effect of 17b-estradiol (E 2 ) stimulation were assessed using quantitative PCR and western blotting. We have found that the mRNA of Obr was dynamically expressed during the differentiation of ATDC5 cells over 21 days. Application of E 2 (10 K7 M) at day 14 for 48 h significantly upregulated OBR mRNA and protein levels (P!0 . 05). The upregulation of Obr mRNA by E 2 was shown to take place in a concentration-dependent manner, with a concentration of 10 K7 M E 2 having the greatest effect. Furthermore, we have confirmed that E 2 affected the phosphorylation of ERK1/2 (MAPK1/MAPK3) in a time-dependent manner where a maximal fourfold change was observed at 10 min following application of E 2 . Finally, pretreatment of the cells with either U0126 (ERK1/2 inhibitor) or ICI 182 780 (ER antagonist) blocked the upregulation of OBR by E 2 and prevented the E 2 -induced phosphorylation of ERK. These data demonstrate, for the first time, the existence of cross talk between estrogen and OBR in the regulation of bone growth whereby estrogen regulates the expression of Obr in growth plate chondrocytes via ERs and the activation of ERK1/2 signaling pathways.

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“…Thus, combining the increased genetic resolution of an F 10 AI line study, with the full range of single-locus and epistatic mapping strategies promises to produce novel insights into the contribution of epistatic interactions to variation in reproductive fatpad weight in mice. Furthermore, the accumulating data on positional candidate genes (e.g., Chehab 2008;Gat-Yablonski and Phillip 2008;Ichihara and Yamada 2008;Cheverud et al 2010) provides the opportunity to explore functional hypotheses for identified loci and their interactions.…”

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confidence: 99%

Mapping the Epistatic Network Underlying Murine Reproductive Fatpad Variation

Jarvis

Cheverud

2011

Genetics

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Genome-wide mapping analyses are now commonplace in many species and several networks of interacting loci have been reported. However, relatively few details regarding epistatic interactions and their contribution to complex trait variation in multicellular organisms are available and the identification of positional candidate loci for epistatic QTL (epiQTL) is hampered, especially in mammals, by the limited genetic resolution inherent in most study designs. Here we further investigate the genetic architecture of reproductive fatpad weight in mice using the F 10 generation of the LG,SM advanced intercross (AI) line. We apply multiple mapping techniques including a single-locus model, locus-specific composite interval mapping (CIM), and tests for multiple QTL per chromosome to the 12 chromosomes known to harbor single-locus QTL (slQTL) affecting obesity in this cross. We also perform a genome-wide scan for pairwise epistasis. Using this combination of approaches we detect 199 peaks spread over all 19 autosomes, which potentially contribute to trait variation including all eight original F 2 loci (Adip1-8), novel slQTL peaks on chromosomes 7 and 9, and several novel epistatic loci. Extensive epistasis is confirmed involving both slQTL confidence intervals (C.I.) as well as regions that show no significant additive or dominance effects. These results provide important new insights into mapping complex genetic architectures and the role of epistasis in complex trait variation.

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Leptin and regulation of linear growth

Abstract: Leptin stimulates linear growth by regulating the energy balance of the organism and by stimulating the production and secretion of growth hormone from the hypothalamus; at the same time, it is involved with bone remodeling and has a direct effect on the chondrocytes of the growth plate.

Cited by 79 publications

References 53 publications

Leptin in human physiology and pathophysiology

Leptin in human physiology and pathophysiology

Estrogen stimulates leptin receptor expression in ATDC5 cells via the estrogen receptor and extracellular signal-regulated kinase pathways

Mapping the Epistatic Network Underlying Murine Reproductive Fatpad Variation

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