scholarly journals Down regulation of leptin receptor expression and increase the spontaneous unit discharge in arcuate nucleus of hypothalamus in obese rats

2005 ◽  
Vol 18 (5) ◽  
pp. A207-A207
Author(s):  
J CHEN ◽  
S ZHANG ◽  
Y WU ◽  
H CHEN ◽  
Z ZHU
Endocrinology ◽  
2003 ◽  
Vol 144 (5) ◽  
pp. 2016-2024 ◽  
Author(s):  
Gregory J. Morton ◽  
Kevin D. Niswender ◽  
Christopher J. Rhodes ◽  
Martin G. Myers ◽  
James E. Blevins ◽  
...  

Leptin signaling in the hypothalamic arcuate nucleus (ARC) is hypothesized to play an important role in energy homeostasis. To investigate whether leptin signaling limited to this brain area is sufficient to reduce food intake and body weight, we used adenoviral gene therapy to express the signaling isoform of the leptin receptor, leprb, in the ARC of leptin receptor-deficient Koletsky (fak/fak) rats. Successful expression of adenovirus containing leprb (Ad-leprb) selectively in the ARC was documented by in situ hybridization. Using real-time PCR, we further demonstrated that bilateral microinjection of Ad-leprb into the ARC restored low hypothalamic levels of leprb mRNA to values approximating those of wild-type (Fak/Fak) controls. Restored leptin receptor expression in the ARC reduced both mean daily food intake (by 13%) and body weight gain (by 33%) and increased hypothalamic proopiomelanocortin mRNA by 65% while decreasing neuropeptide Y mRNA levels by 30%, relative to fak/fak rats injected with a control adenovirus (Ad-lacZ) (P < 0.05 for each comparison). In contrast, Ad-leprb delivery to either the lateral hypothalamic area of fak/fak rats or to the ARC of wild-type Fak/Fak rats had no effect on any of these parameters. These findings collectively support the hypothesis that leptin receptor signaling in the ARC is sufficient to mediate major effects of leptin on long-term energy homeostasis. Adenoviral gene therapy is thus a viable strategy with which to study the physiological importance of specific molecules acting in discrete brain areas.


2012 ◽  
Vol 40 (03) ◽  
pp. 511-520 ◽  
Author(s):  
Meirong Gong ◽  
Xinjun Wang ◽  
Zhen Mao ◽  
Qinhua Shao ◽  
Xiaoren Xiang ◽  
...  

In the present study, the effects of electroacupuncture (EA) on body weight and sensitivity of leptin in diet-induced obese rats were examined and the underlying mechanisms were explored. After feeding with high-fat (HIF) diet for 12 weeks, the diet-induced obese rats received electroacupuncture stimulation three times per week for four weeks. The expression of the leptin receptor in the hypothalamus was measured using immunohistochemistry. The plasma leptin was detected with ELISA. The leptin and leptin receptor mRNA was examined with real-time PCR. Results showed that electroacupuncture treatment led to a reduction of body weight, decrease in the plasma leptin levels, and an increase in leptin receptor expression in the hypothalamus. Our results suggested that regulating the expression of leptin and the leptin receptor might be one of the molecular mechanisms underlying the reduction of body weight in diet-induced obese rats by electroacupuncture treatment.


2003 ◽  
Vol 28 (05) ◽  
Author(s):  
C Peiser ◽  
K Hupe-Sodmann ◽  
RE Lang

2015 ◽  
Author(s):  
Narjes Nasiri Ansari ◽  
Eliana Spilioti ◽  
Vasiliki Kalotychou ◽  
Geena Dalagiorgou ◽  
Paraskevi Moutsatsou ◽  
...  

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1870-P
Author(s):  
SHELLY NASON ◽  
TEAYOUN KIM ◽  
JESSICA P. ANTIPENKO ◽  
BRIAN FINAN ◽  
RICHARD DIMARCHI ◽  
...  

2021 ◽  
Vol 14 (1) ◽  
pp. 52
Author(s):  
Kirsty Hamilton ◽  
Jenni Harvey

It is widely accepted that the endocrine hormone leptin controls food intake and energy homeostasis via activation of leptin receptors expressed on hypothalamic arcuate neurons. The hippocampal formation also displays raised levels of leptin receptor expression and accumulating evidence indicates that leptin has a significant impact on hippocampal synaptic function. Thus, cellular and behavioural studies support a cognitive enhancing role for leptin as excitatory synaptic transmission, synaptic plasticity and glutamate receptor trafficking at hippocampal Schaffer collateral (SC)-CA1 synapses are regulated by leptin, and treatment with leptin enhances performance in hippocampus-dependent memory tasks. Recent studies indicate that hippocampal temporoammonic (TA)-CA1 synapses are also a key target for leptin. The ability of leptin to regulate TA-CA1 synapses has important functional consequences as TA-CA1 synapses are implicated in spatial and episodic memory processes. Moreover, degeneration is initiated in the TA pathway at very early stages of Alzheimer’s disease, and recent clinical evidence has revealed links between plasma leptin levels and the incidence of Alzheimer’s disease (AD). Additionally, accumulating evidence indicates that leptin has neuroprotective actions in various AD models, whereas dysfunctions in the leptin system accelerate AD pathogenesis. Here, we review the data implicating the leptin system as a potential novel target for AD, and the evidence that boosting the hippocampal actions of leptin may be beneficial.


2013 ◽  
Vol 217 (3) ◽  
pp. 303-315 ◽  
Author(s):  
M B Mazzucco ◽  
R Higa ◽  
E Capobianco ◽  
M Kurtz ◽  
A Jawerbaum ◽  
...  

Metabolic alterations in obese and overweight mothers impact the placenta and the fetus, leading to anomalies in fetal growth and lipid accretion. The primary aim of the study was to examine the effect of a saturated fat-rich diet (FD) on growth, lipid accretion, and lipases, leptin and leptin receptor (ObR) expression in the placenta and fetal liver. We also aimed to find a role for fetal leptin in the modulation of placental and fetal liver lipase and ObR expression. Six-week-old rats were fed with a standard rat chow (control) or a 25% FD for 7 weeks until mating and during pregnancy. Also, in a group of control rats, fetuses were injected with leptin on days 19, 20, and 21 of pregnancy. On day 21, we assessed lipidemia, insulinemia, and leptinemia in mothers and fetuses. In the placenta and fetal liver, lipid concentration was assessed by thin layer chromatography (TLC) and the gene expression of lipoprotein lipase (LPL), endothelial lipase, insulin receptor (Insr), leptin, and ObR by RT-PCR. The FD induced hypertriglyceridemia and hyperleptinemia (P<0.01) in mothers and fetuses, an increase in maternal (P<0.05) and fetal weight (P<0.01), overaccumulation of lipids in fetal liver (P<0.01), and enhanced leptin expression in the placenta and fetal liver (P<0.05). Placental expression of IR and LPL was increased (P<0.05), and ObR decreased (P<0.05) in the FD group. Fetal administration of leptin induced the placental and fetal liver downregulation of ObR (P<0.05) and upregulation of LPL expression (P<0.05). The FD led to increased fetal lipid levels, which may result from high maternal lipid availability and fetal leptin effects.


2007 ◽  
Vol 292 (1) ◽  
pp. R242-R252 ◽  
Author(s):  
Chantacha Anukulkitch ◽  
Alexandra Rao ◽  
Frank R. Dunshea ◽  
Dominique Blache ◽  
Gerald A. Lincoln ◽  
...  

We studied the effects of photoperiod on metabolic profiles, adiposity, and gene expression of hypothalamic appetite-regulating peptides in gonad-intact and castrated Soay rams. Groups of five to six animals were studied 6, 18, or 30 wk after switching from long photoperiod (LP: 16 h of light) to short photoperiod (SP: 8 h of light). Reproductive and metabolic indexes were measured in blood plasma. Expression of neuropeptide Y (NPY), proopiomelanocortin (POMC), and leptin receptor (ObRb) in the arcuate nucleus was measured using in situ hybridization. Testosterone levels of intact animals were low under LP, increased to a peak at 16 wk under SP, and then declined. Voluntary food intake (VFI) was high under LP in both intact and castrated animals, decreased to a nadir at 12–16 wk under SP, and then recovered, but only in intact rams as the reproductive axis became photorefractory to SP. NPY gene expression varied positively and POMC expression varied negatively with the cycle in VFI, with differences between intact and castrate rams in the refractory phase. ObRb expression decreased under SP, unrelated to changes in VFI. Visceral fat weight also varied between the intact and castrated animals across the cycle. We conclude that 1) photoperiodic changes in VFI reflect changes in NPY and POMC gene expression, 2) changes in ObRb gene expression are not necessarily determinants of changes in VFI, 3) gonadal status affects the pattern of VFI that changes with photoperiod, and 4) in the absence of gonadal factors, animals can eat less but gain adiposity.


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