Disease relevance of OB

• We speculate that this leptin-mediated stimulation of angiogenesis might represent not only a key event in the settlement of obesity but also may contribute to the modulation of growth under physiological and pathophysiological conditions in other tissues [1].
• These data indicate that leptin is expressed in pigs, the expressed protein is secreted into the bloodstream, and obese swine express higher levels of leptin mRNA and protein than nonobese swine at similar body weight [2].
• Toxicity rankings for the fungal toxins were consistent with in vivo studies and were, in order of most to least toxic, OA > OB > CIT [3].
• The effects of birth weight and postnatal growth patterns on fat depth and plasma leptin concentrations in juvenile and adult pigs [4].
• Our data indicate that during acute endotoxemia (1-10 h after injection), leptin gene expression is decreased compared with ad libitum fed animals and is more closely related to energy homeostasis than cytokine profiles in plasma [5].

Psychiatry related information on OB

• These findings indicate that there are distinct OBR-IR neuronal populations in the porcine hypothalamus and leptin not only plays an integrative role in feeding behavior, but also in neuroendocrine activity [6].
• CONCLUSION: These findings support the idea that leptin might play a role in the regulation of the hypothalamic-pituitary axis activity, and consequently in the control of pregnancy during critical period of embryo implantation in the pig [7].

High impact information on OB

• The adipocyte-derived cytokine leptin is thought to play a key role in the control of satiety and energy expenditure [1].
• These results indicate that leptin, via activation of the endothelial Ob-R, generates a growth signal involving a tyrosine kinase-dependent intracellular pathway and promotes angiogenic processes [1].
• Because adipogenesis and angiogenesis are tightly correlated during the fat mass development, we tested the hypothesis that leptin is able to modulate the growth of the vasculature [1].
• Application of the K(ATP) channel opener diazoxide or the ob gene product leptin mimicked the effect of glucose removal in a reversible manner; moreover, hyperpolarizations evoked by either agent were inhibited by tolbutamide [8].
• Of the polymorphisms reported for exonic, intronic, and promoter regions of the leptin gene, 16 have been included in association studies in humans, 19 in cattle, and 6 (all exonic or intronic) in pigs [9].

Chemical compound and disease context of OB

• Changes in body weight or nutritional status are characterized by altered adipocyte function a reduction in adipose tissue leptin expression, serum leptin concentrations and a concurrent decrease in LH secretion [10].
• Effects of intraperitoneal vitamin E, melatonin and aprotinin on leptin expression in the guinea pig eye during experimental uveitis [11].

Biological context of OB

• Leptin regulates GH gene expression and secretion and nitric oxide production in pig pituitary cells [12].
• Leptin is a key mediator of signals regulating food intake and energy expenditure and exerts potent immunomodulatory effects [13].
• Genetic polymorphisms in the leptin gene and their association with fatness in four pig breeds [14].
• Assignment of the porcine obese (leptin) gene to chromosome 18 by linkage analysis of a new PCR-based polymorphism [15].
• The results suggest that the serum leptin level and leptin gene expression in adipose tissue highly correlate with adiposity [16].

Anatomical context of OB

• Expression of Ob-R has been reported in human and mouse oocytes; however, the physiological role of leptin during follicular development and oocyte maturation is largely unknown [17].
• The adipose tissue glucose transporter 4, fatty acid synthase, and leptin transcript concentrations were greater (P < .05) in obese than in lean pigs [18].
• Leptin is a 16-kDa protein secreted by adipocytes that has been proposed to regulate feed intake in mice, rats, and humans [2].
• Leptin concentrations in plasma and follicular fluid from prepubertal gilts as influenced by fasting, refeeding and insulin [19].
• For assessment of porcine leptin gene expression, total RNA was extracted from the subcutaneous adipose tissue of genetically selected high backfat pigs and from contemporary crossbred swine [2].

Associations of OB with chemical compounds

• GH gene expression was significantly increased (at least P < 0.05) by hexarelin, GHRH, and leptin (1000 and 100 nM) after 24 h of treatment [12].
• Although the addition of sodium nitroprusside, a spontaneous liberator of NO, stimulated GH release from PBMCs, leptin had no additive or synergistic effect on sodium nitroprusside-induced GH production [13].
• Leptin led to a nitric oxide (NO) synthase (NOS)-specific, dose-dependent increase in NO production from PBMCs because leptin-induced NO release was blocked by the addition of the NOS inhibitor Nomega-Nitro-l-arginine methyl ester and protein kinase C (PKC) inhibitor calphostin C [13].
• MEASUREMENTS: Plasma insulin-like growth factor 1 (IGF-1), insulin, leptin, nonesterified fatty acids, triglycerides (TGs) and glucose were determined at sexual maturity and at young adulthood [20].
• Purified recombinant human, mouse, rat, pig, and chicken leptin proteins were separated by polyacrylamide gel electrophoresis (SDS-PAGE) and electro-blotted onto PVDF membranes [21].

Physical interactions of OB

• Leptin had a biphasic effect on the abundance of membrane-bound and transcriptionally active forms of SREBP1 [22].

Regulatory relationships of OB

• Expression of UCP2 was induced by leptin (100 ng/mL; P<0.05) [23].
• The present study also showed that H89 (a PKA inhibitor) moderately, but significantly, inhibited leptin-induced ERK and TH mRNA [24].
• We have previously shown that murine recombinant leptin directly stimulates catecholamine synthesis through the long form of the leptin receptor (Ob-Rb) expressed in cultured porcine chromaffin cells [24].
• StAR transcription was also increased by the low dose of leptin and was further upregulated in the presence of the SREBP plasmid [22].
• Dex-induced increases in leptin mRNA levels and AD-3 cell numbers were blocked completely by the addition of transforming growth factor-beta (TGF-beta) to FBS+Dex-treated cultures [25].

Other interactions of OB

• These data also support a probable role for local immune-derived GH in mediating some of the pleiotropic actions of leptin [13].
• Western blotting was used to evaluate serum levels of porcine leptin in genetically selected high backfat and contemporary, crossbred pigs [2].
• Only at the highest dose (200 ng/ml) when leptin was added with IGF-I did P4 secretion decrease with no effect on the caspase-3 activity [26].
• The LPL and leptin increased continuously [27].
• Regression analysis indicated that UCP3 expression was differentially associated with IGF-1, leptin, and insulin [28].

Analytical, diagnostic and therapeutic context of OB

• Western blots were developed employing the leptin-specific peptide antiserum with an alkaline-phosphatase-conjugated anti-rabbit IgG second antibody chromogenic system [21].
• Successful RT-PCR resulted in development of a cDNA clone to the full length coding region of porcine leptin [2].
• However, with this assay we were able to detect native leptin protein in an enriched fraction prepared from chicken plasma using a combination of gel filtration and ion exchange column chromatography [21].
• Sequence analysis of the 258 bp product from the hypothalamus and pituitary confirmed 99% homology with the corresponding region of porcine leptin cDNA sequence [29].
• The hormonal regulation of leptin mRNA expression and the association between leptin expression and adipocyte differentiation were examined in primary cultures of porcine S-V cells with Northern blot and immunocytochemical analysis [25].

References