Diet composition, not calorie intake, rapidly alters intrinsic excitability of hypothalamic AgRP/NPY neurons in mice

Wei, Wei; Pham, Kevin; Gammons, Jesse; Sutherland, Daniel E.; Liu, Yanyun; Smith, Alana; Kaczorowski, Catherine C.; O’Connell, Kathryn A

doi:10.1038/srep16810

Cited by 46 publications

(74 citation statements)

References 46 publications

(78 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…HFD feeding seems to increase AgRP neuronal activity (39–41) but does not seem to worsen the metabolic phenotype of AgRP IR KO mice, possibly because their AgRP neurons are already disinhibited by the lack of insulin signaling. Although insulin appears to also reduce the firing rate of POMC neurons, HFD feeding increases POMC neuronal activity and/or melanocortinergic tone (42–45), and a lack of insulin signaling in POMC neurons potentiates the dysmetabolic effects of HFD feeding.…”

Section: Discussionmentioning

confidence: 99%

Insulin Receptor Signaling in POMC, but Not AgRP, Neurons Controls Adipose Tissue Insulin Action

et al. 2017

View full text Add to dashboard Cite

Insulin is a key regulator of adipose tissue lipolysis, and impaired adipose tissue insulin action results in unrestrained lipolysis and lipotoxicity, which are hallmarks of the metabolic syndrome and diabetes. Insulin regulates adipose tissue metabolism through direct effects on adipocytes and through signaling in the central nervous system by dampening sympathetic outflow to the adipose tissue. Here we examined the role of insulin signaling in agouti-related protein (AgRP) and pro-opiomelanocortin (POMC) neurons in regulating hepatic and adipose tissue insulin action. Mice lacking the insulin receptor in AgRP neurons (AgRP IR KO) exhibited impaired hepatic insulin action because the ability of insulin to suppress hepatic glucose production (hGP) was reduced, but the ability of insulin to suppress lipolysis was unaltered. To the contrary, in POMC IR KO mice, insulin lowered hGP but failed to suppress adipose tissue lipolysis. High-fat diet equally worsened glucose tolerance in AgRP and POMC IR KO mice and their respective controls but increased hepatic triglyceride levels only in POMC IR KO mice, consistent with impaired lipolytic regulation resulting in fatty liver. These data suggest that although insulin signaling in AgRP neurons is important in regulating glucose metabolism, insulin signaling in POMC neurons controls adipose tissue lipolysis and prevents high-fat diet–induced hepatic steatosis.

show abstract

Section: Discussionmentioning

confidence: 99%

Insulin Receptor Signaling in POMC, but Not AgRP, Neurons Controls Adipose Tissue Insulin Action

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The rapid onset of behavioral arrhythmicity indicates that it is likely to occur by a mechanism independent of clock gene regulation, which would take longer to adapt. Highly palatable foods or particular nutrient compositions can directly and rapidly signal to orexigenic centers (126). The HFD in particular directly affects appetite regulating centers in the arcuate nucleus as well as the regions associated with hedonic/reward stimulation that influence food-seeking behavior (127)(128)(129).…”

Section: Altered Rhythms In Feeding Behaviormentioning

confidence: 99%

Feeding Rhythms and the Circadian Regulation of Metabolism

2020

View full text Add to dashboard Cite

The molecular circadian clock regulates metabolic processes within the cell, and the alignment of these clocks between tissues is essential for the maintenance of metabolic homeostasis. The possibility of misalignment arises from the differential responsiveness of tissues to the environmental cues that synchronize the clock (zeitgebers). Although light is the dominant environmental cue for the master clock of the suprachiasmatic nucleus, many other tissues are sensitive to feeding and fasting. When rhythms of feeding behavior are altered, for example by shift work or the constant availability of highly palatable foods, strong feedback is sent to the peripheral molecular clocks. Varying degrees of phase shift can cause the systemic misalignment of metabolic processes. Moreover, when there is a misalignment between the endogenous rhythms in physiology and environmental inputs, such as feeding during the inactive phase, the body's ability to maintain homeostasis is impaired. The loss of phase coordination between the organism and environment, as well as internal misalignment between tissues, can produce cardiometabolic disease as a consequence. The aim of this review is to synthesize the work on the mechanisms and metabolic effects of circadian misalignment. The timing of food intake is highlighted as a powerful environmental cue with the potential to destroy or restore the synchrony of circadian rhythms in metabolism.

show abstract

“…The ARC is a main hub for the central integration of metabolic signals, whereby two neuronal populations are important: pro‐opiomelanocortin neurons inhibit, whereas neuropeptide Y/agouti‐related protein neurons increase appetite . Therefore, many studies investigated the effect of timing of food intake on the ARC oscillator.…”

Section: Functional Studies Of Extra‐scn Oscillatorsmentioning

confidence: 99%

Regulation and function of extra‐SCN circadian oscillators in the brain

2020

View full text Add to dashboard Cite

Most organisms evolved endogenous, so called circadian clocks as internal timekeeping mechanisms allowing them to adapt to recurring changes in environmental demands brought about by 24-hour rhythms such as the light-dark cycle, temperature variations or changes in humidity. The mammalian circadian clock system is based on cellular oscillators found in all tissues of the body that are organized in a hierarchical fashion. A master pacemaker located in the suprachiasmatic nucleus (SCN) synchronizes peripheral tissue clocks and extra-SCN oscillators in the brain with each other and with external time. Different time cues (so called Zeitgebers) such as light, food intake, activity and hormonal signals reset the clock system through the SCN or by direct action at the tissue clock level. While most studies on non-SCN clocks so far have focused on peripheral tissues, several extra-SCN central oscillators were characterized in terms of circadian rhythm regulation and output. Some of them are directly innervated by the SCN pacemaker, while others receive indirect input from the SCN via other neural circuits or extra-brain structures. The specific physiological function of these non-SCN brain oscillators as well as their role in the regulation of the circadian clock network remains understudied. In this review we summarize our current knowledge about the regulation and function of extra-SCN circadian oscillators in different brain regions and devise experimental approaches enabling us to unravel the organization of the circadian clock network in the central nervous system. K E Y W O R D S brain, circadian clock, clock gene, CNS, entrainment 2 of 14 | BEGEMANN Et Al.major depression or cardiovascular disorders are promoted by chronodisruption, that is, the perturbation of internal clock function or of the alignment of these clocks with external time. 4 Besides shift work, other chronodisruptive factors are sleep curtailment, high-energy diets or mistimed eating patterns, and nocturnal light pollution. 5,6 Resetting stimuli (eg light)Resetting stimuli (eg PUFAs) Resetting stimuli (eg NO/CO) RORE D-box E-box CLOCK BMAL1 REV-ERBs RORs DBP NFIL3 PERs CRYs CCGsHow to cite this article: Begemann K, Neumann A-M, Oster H. Regulation and function of extra-SCN circadian oscillators in the brain. Acta Physiol.

show abstract

Diet composition, not calorie intake, rapidly alters intrinsic excitability of hypothalamic AgRP/NPY neurons in mice

Cited by 46 publications

References 46 publications

Insulin Receptor Signaling in POMC, but Not AgRP, Neurons Controls Adipose Tissue Insulin Action

Insulin Receptor Signaling in POMC, but Not AgRP, Neurons Controls Adipose Tissue Insulin Action

Feeding Rhythms and the Circadian Regulation of Metabolism

Regulation and function of extra‐SCN circadian oscillators in the brain

Contact Info

Product

Resources

About