High-fat diet induces time-dependent synaptic plasticity of the lateral hypothalamus

Autor: Michiru Hirasawa, Matthew P. Parsons, Lisa Z. Fang, Victoria Linehan
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
HFD
high-fat diet
Patch-Clamp Techniques
Lateral hypothalamus
Action Potentials
Energy homeostasis
Rats
Sprague-Dawley
Mice
0302 clinical medicine
Postsynaptic potential
Homeostasis
Neurons
2. Zero hunger
Hypothalamic Hormones
Neuronal Plasticity
digestive
oral
and skin physiology
Diet-induced obesity
Intracellular Signaling Peptides and Proteins
High-fat diet
DNQX
6
7-Dinitroquinoxaline-2
3-dione
LH
lateral hypothalamus
MCH
melanin-concentrating hormone
Excitatory postsynaptic potential
Original Article
D-AP5
D-(−)-2-Amino-5-phosphonopentanoic acid
hormones
hormone substitutes
and hormone antagonists
lcsh:Internal medicine
medicine.medical_specialty
030209 endocrinology & metabolism
PPR
paired pulse ratio
Neurotransmission
Biology
Diet
High-Fat
Melanin-concentrating hormone
03 medical and health sciences
Internal medicine
medicine
Animals
mEPSC
miniature excitatory postsynaptic current
Obesity
Synaptic transmission
Patch clamp
lcsh:RC31-1245
Molecular Biology
Melanins
Orexins
eEPSC
evoked excitatory postsynaptic current
IPSC
inhibitory postsynaptic current
CV
coefficient of variation
DIO
diet-induced obesity
ORX
orexin
Cell Biology
mIPSC
miniature inhibitory postsynaptic current
Rats
EPSC
excitatory postsynaptic current
Orexin
Mice
Inbred C57BL
Pituitary Hormones
030104 developmental biology
Endocrinology
Hypothalamic Area
Lateral
Synaptic plasticity
ACSF
artificial cerebrospinal fluid
NSNA
non-stationary noise analysis
Energy Metabolism
Zdroj: Molecular Metabolism, Vol 36, Iss, Pp-(2020)
Molecular Metabolism
ISSN: 2212-8778
DOI: 10.1016/j.molmet.2020.100977
Popis: Objective Orexin (ORX) and melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus are critical regulators of energy homeostasis and are thought to differentially contribute to diet-induced obesity. However, it is unclear whether the synaptic properties of these cells are altered by obesogenic diets over time. Methods Rats and mice were fed a control chow or palatable high-fat diet (HFD) for various durations and then synaptic properties of ORX and MCH neurons were examined using exvivo whole-cell patch clamp recording. Confocal imaging was performed to assess the number of excitatory synaptic contacts to these neurons. Results ORX neurons exhibited a transient increase in spontaneous excitatory transmission as early as 1 day up to 1 week of HFD, which returned to control levels with prolonged feeding. Conversely, HFD induced a delayed increase in excitatory synaptic transmission to MCH neurons, which progressively increased as HFD became chronic. This increase occurred before the onset of significant weight gain. These synaptic changes appeared to be due to altered postsynaptic sensitivity or the number of active synaptic contacts depending on cell type and feeding duration. However, HFD induced no change in inhibitory transmission in either cell type at any time point. Conclusions These results suggest that the effects of HFD on feeding-related neurons are cell type-specific and dynamic. This highlights the importance of considering the feeding duration for research and weight loss interventions. ORX neurons may contribute to early hyperphagia, whereas MCH neurons may play a role in the onset and long-term maintenance of diet-induced obesity.
Highlights • High-fat diet increases excitatory transmission to orexin and MCH neurons. • Increased excitatory drive to orexin neurons occurs within the first week but is transient. • Excitatory synapses to MCH neurons increase with prolonged high-fat diet. • Excitatory changes in MCH neurons are delayed but precede significant weight gain. • These synaptic changes may contribute to the development and the maintenance of obesity.
Databáze: OpenAIRE
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