Andras Leko, M.D., Ph.D.

@article{pmid38796563,

title = {Genetic or pharmacological GHSR blockade has sexually dimorphic effects in rodents on a high-fat diet},

author = {András H Lékó and Adriana Gregory-Flores and Renata C N Marchette and Juan L Gomez and Janaina C M Vendruscolo and Vez Repunte-Canonigo and Vicky Choung and Sara L Deschaine and Kimberly E Whiting and Shelley N Jackson and Maria Paula Cornejo and Mario Perello and Zhi-Bing You and Michael Eckhaus and Karuna Rasineni and Kim D Janda and Barry Zorman and Pavel Sumazin and George F Koob and Michael Michaelides and Pietro P Sanna and Leandro F Vendruscolo and Lorenzo Leggio},

doi = {10.1038/s42003-024-06303-5},

issn = {2399-3642},

year  = {2024},

date = {2024-05-01},

urldate = {2024-05-01},

journal = {Commun Biol},

volume = {7},

number = {1},

pages = {632},

abstract = {The stomach-derived hormone ghrelin regulates essential physiological functions. The ghrelin receptor (GHSR) has ligand-independent actions; therefore, GHSR gene deletion may be a reasonable approach to investigate the role of this system in feeding behaviors and diet-induced obesity (DIO). Here, we investigate the effects of a long-term (12-month) high-fat (HFD) versus regular diet on obesity-related measures in global GHSR-KO and wild-type (WT) Wistar male and female rats. Our main findings are that the GHSR gene deletion protects against DIO and decreases food intake during HFD in male but not in female rats. GHSR gene deletion increases thermogenesis and brain glucose uptake in male rats and modifies the effects of HFD on brain glucose metabolism in a sex-specific manner, as assessed with small animal positron emission tomography. We use RNA-sequencing to show that GHSR-KO rats have upregulated expression of genes responsible for fat oxidation in brown adipose tissue. Central administration of a novel GHSR inverse agonist, PF-5190457, attenuates ghrelin-induced food intake, but only in male, not in female mice. HFD-induced binge-like eating is reduced by inverse agonism in both sexes. Our results support GHSR as a promising target for new pharmacotherapies for obesity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33546359,

title = {Transcriptome Sequencing in the Preoptic Region of Rat Dams Reveals a Role of Androgen Receptor in the Control of Maternal Behavior},

author = {András H Lékó and Rashmi Kumari and Fanni Dóra and Dávid Keller and Edina B Udvari and Vivien Csikós and Éva Renner and Arpád Dobolyi},

url = {https://pubmed.ncbi.nlm.nih.gov/33546359/},

doi = {10.3390/ijms22041517},

issn = {1422-0067},

year  = {2021},

date = {2021-02-01},

urldate = {2021-02-01},

journal = {Int J Mol Sci},

volume = {22},

number = {4},

abstract = {(1) Background: Preoptic region of hypothalamus is responsible to control maternal behavior, which was hypothesized to be associated with gene expressional changes. (2) Methods: Transcriptome sequencing was first applied in the preoptic region of rat dams in comparison to a control group of mothers whose pups were taken away immediately after parturition and did not exhibit caring behavior 10 days later. (3) Results: Differentially expressed genes were found and validated by quantitative RT-PCR, among them NACHT and WD repeat domain containing 1 (Nwd1) is known to control androgen receptor (AR) protein levels. The distribution of Nwd1 mRNA and AR was similar in the preoptic area. Therefore, we focused on this steroid hormone receptor and found its reduced protein level in rat dams. To establish the function of AR in maternal behavior, its antagonist was administered intracerebroventricularly into mother rats and increased pup-directed behavior of the animals. (4) Conclusions: AR levels are suppressed in the preoptic area of mothers possibly mediated by altered Nwd1 expression in order to allow sustained high-level care for the pups. Thus, our study first implicated the AR in the control of maternal behaviors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28611445,

title = {Insulin-like growth factor I and its binding protein-3 are regulators of lactation and maternal responsiveness},

author = {András H Lékó and Melinda Cservenák and Éva Rebeka Szabó and János Hanics and Alán Alpár and Árpád Dobolyi},

url = {https://pubmed.ncbi.nlm.nih.gov/28611445/},

doi = {10.1038/s41598-017-03645-5},

issn = {2045-2322},

year  = {2017},

date = {2017-01-01},

urldate = {2017-01-01},

journal = {Sci Rep},

volume = {7},

number = {1},

pages = {3396},

abstract = {Adaptation to motherhood includes maternal behaviour and lactation during the postpartum period. The major organizing centres of maternal behaviour and lactation are located in the hypothalamic medial preoptic area (MPOA) and the arcuate nucleus, respectively. Insulin-like growth factor I (IGF-I) is an effector of the growth hormone axis; however, its function in the brain is largely unexplored. We identified increased maternal IGF binding protein-3 (IGFBP-3) expression in preoptic rat microarray data and confirmed it by RT-PCR. In situ hybridization histochemistry showed markedly elevated IGFBP-3 expression in the MPOA and the arcuate nucleus in rat dams. Prolonged intracerebroventricular injection of IGF-I or antagonism of brain IGFBP-3 with an inhibitor (NBI-31772) using osmotic minipumps increased pup retrieval time, suggesting reduced maternal motivation. Suckling-induced prolactin release and pup weight gain were also suppressed by IGF-I, suggesting reduced lactation. In addition, IGF-I-induced tyrosine hydroxylase expression and its specific phosphorylation in tuberoinfundibular dopaminergic neurons suppress prolactin secretion. Thus, IGF-I may inhibit both behavioural and lactational alterations in mothers. Neurons in the MPOA and arcuate nuclei express IGFBP-3 during the postpartum period to neutralize IGF-I effects. IGFBP-3 can prevent the blockade of maternal behaviour and lactation exerted by IGF-I, suggesting a novel modulatory mechanism underlying the behavioural and hormonal effects during central maternal adaptations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}