Hormonal regulation of leptin receptor expression in primary cultures of porcine hepatocytes

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.

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

American Journal of Hypertension ◽

10.1016/j.amjhyper.2005.03.567 ◽

2005 ◽

Vol 18 (5) ◽

pp. A207-A207

Author(s):

J CHEN ◽

S ZHANG ◽

Y WU ◽

H CHEN ◽

Z ZHU

Keyword(s):

Arcuate Nucleus ◽

Leptin Receptor ◽

Receptor Expression ◽

Down Regulation ◽

Unit Discharge ◽

Obese Rats

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Saturated fat-rich diet increases fetal lipids and modulates LPL and leptin receptor expression in rat placentas

Journal of Endocrinology ◽

10.1530/joe-13-0021 ◽

2013 ◽

Vol 217 (3) ◽

pp. 303-315 ◽

Cited By ~ 17

Author(s):

M B Mazzucco ◽

R Higa ◽

E Capobianco ◽

M Kurtz ◽

A Jawerbaum ◽

...

Keyword(s):

Leptin Receptor ◽

Fetal Liver ◽

Liver Lipid ◽

Saturated Fat ◽

Receptor Expression ◽

Lipid Concentration ◽

Old Rats ◽

Liver Lipid Concentration ◽

Leptin Expression ◽

Layer Chromatography

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.

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Phlorotannins from Ecklonia cava Attenuates Palmitate-Induced Endoplasmic Reticulum Stress and Leptin Resistance in Hypothalamic Neurons

Marine Drugs ◽

10.3390/md17100570 ◽

2019 ◽

Vol 17 (10) ◽

pp. 570 ◽

Cited By ~ 5

Author(s):

Seyeon Oh ◽

Myeongjoo Son ◽

Junwon Choi ◽

Chang Hu Choi ◽

Kook Yang Park ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Er Stress ◽

Leptin Receptor ◽

Saturated Fatty Acids ◽

Receptor Expression ◽

Leptin Resistance ◽

Ecklonia Cava ◽

Hypothalamic Neurons ◽

Potent Effect ◽

Stress Markers

Leptin resistance in the hypothalamus has an essential role in obesity. Saturated fatty acids such as palmitate bind to Toll-like receptor 4 (TLR4) and lead to endoplasmic reticulum (ER) stress and leptin resistance. In this study, we evaluated whether extracts of Ecklonia cava would attenuate the ER stress induced by palmitate and reduce leptin resistance in hypothalamic neurons and microglia. We added palmitate to these cells to mimic the environment induced by high-fat diet in the hypothalamus and evaluated which of the E. cava phlorotannins—dieckol (DK), 2,7-phloroglucinol-6,6-bieckol (PHB), pyrogallol-phloroglucinol-6,6-bieckol (PPB), or phlorofucofuroeckol-A (PFFA)—had the most potent effect on attenuating leptin resistance. TLR4 and NF-κB expression induced by palmitate was attenuated most effectively by PPB in both hypothalamic neurons and microglia. ER stress markers were increased by palmitate and were attenuated by PPB in both hypothalamic neurons and microglia. Leptin resistance, which was evaluated as an increase in SOCS3 and a decrease in STAT3 with leptin receptor expression, was increased by palmitate and was decreased by PPB in hypothalamic neurons. The culture medium from palmitate-treated microglia increased leptin resistance in hypothalamic neurons and this resistance was attenuated by PPB. In conclusion, PPB attenuated leptin resistance by decreasing ER stress in both hypothalamic neurons and microglia.

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