Dataset Information

Differential physiological responses to central leptin overexpression in male and female rats.

ABSTRACT: Brains of females are more sensitive to the acute catabolic actions of leptin. However, sex differences in the long-term physiological responses to central leptin receptor modulation are unknown. Accordingly, we centrally delivered a viral vector to overexpress leptin (Leptin), a neutral leptin receptor antagonist (Leptin-Antagonist) or a green fluorescence protein (GFP) (Control). We examined chronic changes in body weight and composition in male and female rats. Females displayed greater and sustained responses to Leptin, whereas males rapidly lost physiological effects and developed leptin resistance as confirmed by lower acute leptin-mediated phosphorylation of signal transducer and activator of transcription 3 (P-STAT3). Surprisingly, despite persistent physiological responses, Leptin-females also exhibited reduced acute leptin-mediated P-STAT3, suggesting an onset of leptin resistance near time of death. In line with this interpretation, Leptin-females and Control-females consumed the same amount of food on the last day of the experiment. Both Leptin-Antagonist groups gained similar percentages of their initial body weight and fat mass, whereas only Leptin-Antagonist-females gained lean body mass. Consequently, the lean/fat mass ratio with Leptin-Antagonist was preserved in females and decreased in males, suggesting a deterioration of body composition in males. In summary, the present study establishes that females are more responsive to long-term central leptin overexpression than males and that leptin antagonism has a greater physiological impact in males. The hormone environment may have played a role in these processes; however, future studies are needed to establish whether such physiological responses are mediated by female or male sex hormones.

SUBMITTER: Cote I

PROVIDER: S-EPMC5739960 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Differential physiological responses to central leptin overexpression in male and female rats.

Côté I I Green S M SM Toklu H Z HZ Morgan D D Carter C S CS Tümer N N Scarpace P J PJ

Journal of neuroendocrinology 20171201 12

Brains of females are more sensitive to the acute catabolic actions of leptin. However, sex differences in the long-term physiological responses to central leptin receptor modulation are unknown. Accordingly, we centrally delivered a viral vector to overexpress leptin (Leptin), a neutral leptin receptor antagonist (Leptin-Antagonist) or a green fluorescence protein (GFP) (Control). We examined chronic changes in body weight and composition in male and female rats. Females displayed greater and s ...[more]

PMID: 29044801

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Project description:ObjectiveThe aim of this study is to identify physiological responses of male and female rats to either a short- or long-term administration of two doses of Maca (Lepidium peruvianum) and observe relationships which may exist between groups of hormones and effects mediated by them.DesignThe effect of pre-gelatinized (extruded) organic Maca powder (Maca-GO) was studied on Sprague-Dowley male and female rats (1:1 ratio) receiving two dietary levels of Maca-GO (0.75 g/kg and 7.5 g/kg body weight) and assessed against control during 28 and 90 day laboratory trials on 30 and 60 rats respectively. Blood morphology, biochemistry (hormones, lipids and minerals) and histology of internal organs were determined. Homogenates of skeletal muscles and bones of rats were also analyzed.ResultsMaca-GO has low toxicity (LD=7.5 g/kg) and appears to be safe for short-term and extended use as dietary supplement or as a component of functional dietary and therapeutic preparations. There were different responses of male and female rats to different levels of Maca-GO administered during a short- and a longer-term periodl. When administered at higher dose for extended period of time (90 days), Maca-GO acted as a toner of hormonal processes in adult female rats at increased progesterone and a steady estradiol level, without affecting levels of blood FSH, LH and TSH.ConclusionsObtained results justify further clinical research on use of Maca-GO in sportsmen, physically-active people of both sexes and peri-menopausal women to clarify mechanisms underlaying physiological mode of action of Maca-GO validaet in clinical study on humans. Substantial decrease in blood cortisol levels in a short- and longer-term trial and simultaneous tendency to lower blood ACTH, may indicate antidepressive effect of Maca-GO, which together with reduction in body weight, lowering triglycerides in blood plasma and increasing calcium and phosphorus deposition in bone and muscle tissues is worthy consideration in potential application to women at both, pre- and postmenopausal stage.

Project description:BackgroundUnder caged conditions, birds are affected more severely by environmental stressors such as dietary structure, activity space, human disturbances, and pathogens, which may be reflected in the gene expression in peripheral blood or other tissues. Elucidating the molecular mechanism of these stress responses will help improve animal welfare.ResultsIn the present study, the blood transcriptomes of six male and five female caged magpies (Pica pica) were sequenced, and a total of ~ 100 Gb in clean reads were generated using the Illumina HiSeq 2000 sequencer. A total of 420,291 unigenes were identified after assembly, of which 179,316 were annotated in five databases, 7471 were assigned to 269 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and 566 were assigned to the Clusters of Orthologous Groups (COG) functional classification "defense mechanisms". Analysis of differentially expressed genes (DEGs) showed that 2657 unigenes were differentially expressed between males and females (q < 0.1), and these DEGs were assigned to 45 KEGG pathways involving stress resistance, immunity, energy metabolism, reproduction, lifespan regulation, and diseases. Further analysis revealed that females might be more sensitive to stress through upregulation of c-Jun N-terminal kinases (JNKs) and 5'AMP-activated protein kinase (AMPK), and were also possibly more sensitive to dynamic changes in energy. Females expressed higher major histocompatibility complex (MHC) class II levels than males, enhancing resistance to pathogens, and the DEGs related to reproduction included MAPK, CaMK, CPEB, and Cdc25. The genes related to stress, energy, and immunity were also likely related to the regulation of longevity. The upregulated JNKs in females might prolong lifespan and relieve antioxidant stress. Females may also activate the AMPK pathway and implement dietary restrictions to prolong lifespan, whereas males may upregulate SIRT1 and CRAB to increase lifespan.ConclusionsFemale magpies might be more sensitive to stress and dynamic changes in energy thus enhanced resistance to pathogens, and the genes related to stress, energy, and immunity were also possibly related to the regulation of longevity. Further confirmations with techniques such as RT-qPCR and western blot are necessary to validate the above arguments.

Dataset Information

Differential physiological responses to central leptin overexpression in male and female rats.

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Differential physiological responses to central leptin overexpression in male and female rats.

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