Disrupted hypothalamic
            <scp>CRH</scp>
            neuron responsiveness contributes to diet‐induced obesity

Zhu, Canjun; Xu, Yuanzhong; Jiang, Zhiying; Tian, Jing; Cassidy, Ryan M.; Cai, Zhao-Lin; Shu, Gang; Xu, Yong; Xue, Mingshan; Arenkiel, Benjamin R.; Jiang, Qingyan; Tong, Qingchun

doi:10.15252/embr.201949210

Cited by 19 publications

(17 citation statements)

References 46 publications

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“…Diet is also capable of remodeling circadian rhythms behaviorally, transcriptionally, and metabolically [ 22 , 260 , 272 , 273 ]. For example, feeding mice a ketogenic diet or overexpressing the FGF21 (whose production is stimulated by a ketogenic diet) augments locomotion during the daytime and results in a phase advance in mice [ 183 ].…”

Section: The Role Of Intrinsic Clocks Of the Hypothalamus In Obesimentioning

confidence: 99%

“…For example, feeding mice a ketogenic diet or overexpressing the FGF21 (whose production is stimulated by a ketogenic diet) augments locomotion during the daytime and results in a phase advance in mice [ 183 ]. Mice placed on standard HFD have a profound reorganization of their circadian gene expression and metabolite production, in several metabolic tissues, including liver, adipose tissue, and the CNS [ 22 , 272 , 273 ]. However, hypothalamic PER2::LUC rhythms in the SCN, DMH or ARC appear unaltered under HFD [ 91 ].…”

Section: The Role Of Intrinsic Clocks Of the Hypothalamus In Obesimentioning

confidence: 99%

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Circadian Rhythms of the Hypothalamus: From Function to Physiology

Drunen

Eckel‐Mahan

2021

Clocks & Sleep

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The nearly ubiquitous expression of endogenous 24 h oscillations known as circadian rhythms regulate the timing of physiological functions in the body. These intrinsic rhythms are sensitive to external cues, known as zeitgebers, which entrain the internal biological processes to the daily environmental changes in light, temperature, and food availability. Light directly entrains the master clock, the suprachiasmatic nucleus (SCN) which lies in the hypothalamus of the brain and is responsible for synchronizing internal rhythms. However, recent evidence underscores the importance of other hypothalamic nuclei in regulating several essential rhythmic biological functions. These extra-SCN hypothalamic nuclei also express circadian rhythms, suggesting distinct regions that oscillate either semi-autonomously or independent of SCN innervation. Concurrently, the extra-SCN hypothalamic nuclei are also sensitized to fluctuations in nutrient and hormonal signals. Thus, food intake acts as another powerful entrainer for the hypothalamic oscillators’ mediation of energy homeostasis. Ablation studies and genetic mouse models with perturbed extra-SCN hypothalamic nuclei function reveal their critical downstream involvement in an array of functions including metabolism, thermogenesis, food consumption, thirst, mood and sleep. Large epidemiological studies of individuals whose internal circadian cycle is chronically disrupted reveal that disruption of our internal clock is associated with an increased risk of obesity and several neurological diseases and disorders. In this review, we discuss the profound role of the extra-SCN hypothalamic nuclei in rhythmically regulating and coordinating body wide functions.

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Section: The Role Of Intrinsic Clocks Of the Hypothalamus In Obesimentioning

confidence: 99%

Section: The Role Of Intrinsic Clocks Of the Hypothalamus In Obesimentioning

confidence: 99%

Circadian Rhythms of the Hypothalamus: From Function to Physiology

Drunen

Eckel‐Mahan

2021

Clocks & Sleep

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“…The exception was a reduced energy expenditure exhibited by CRH GHR KO females. High-fat/high-caloric diet disturbs the activity of PVH CRH neurons, leading to decreased energy expenditure [ 74 ]. Intriguingly, it is unknown why the low energy expenditure was observed only in CRH GHR KO female mice.…”

Section: Discussionmentioning

confidence: 99%

Effects of Growth Hormone Receptor Ablation in Corticotropin-Releasing Hormone Cells

Santos

Gusmao

Wasinski

et al. 2021

IJMS

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Corticotropin-releasing hormone (CRH) cells are the dominant neuronal population responsive to the growth hormone (GH) in the paraventricular nucleus of the hypothalamus (PVH). However, the physiological importance of GH receptor (GHR) signaling in CRH neurons is currently unknown. Thus, the main objective of the present study was to investigate the consequences of GHR ablation in CRH-expressing cells of male and female mice. GHR ablation in CRH cells did not cause significant changes in body weight, body composition, food intake, substrate oxidation, locomotor activity, glucose tolerance, insulin sensitivity, counterregulatory response to 2-deoxy-D-glucose and ghrelin-induced food intake. However, reduced energy expenditure was observed in female mice carrying GHR ablation in CRH cells. The absence of GHR in CRH cells did not affect anxiety, circadian glucocorticoid levels or restraint-stress-induced corticosterone secretion and activation of PVH neurons in both male and female mice. In summary, GHR ablation, specifically in CRH-expressing neurons, does not lead to major alterations in metabolism, hypothalamic–pituitary–adrenal axis, acute stress response or anxiety in mice. Considering the previous studies showing that central GHR signaling regulates homeostasis in situations of metabolic stress, future studies are still necessary to identify the potential physiological importance of GH action on CRH neurons.

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“…It was recently reported that fasting-induced activation of AMP-activated kinase (AMPK) causes increased activity of PVH CRH neurons, which contributes to a preference for a high-carbohydrate diet (nutrition) over a HFD (palatability) under fasting conditions 64 . A more recent study demonstrated that HFD feeding blunted the responsiveness of PVH CRH neurons and that mice with blunted PVH CRH neuronal responsiveness were more likely to develop HFD-induced obesity 65 . Overall, these studies suggest that PVH CRH neurons may participate in the fine tuning of food intake rather than control food intake per se.…”

Section: Role Of the Hpa Axis And Crh Neuronsmentioning

confidence: 99%

Neuroendocrine control of appetite and metabolism

Yoo

Sohn

2021

Exp Mol Med

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Body homeostasis is predominantly controlled by hormones secreted by endocrine organs. The central nervous system contains several important endocrine structures, including the hypothalamic-pituitary axis. Conventionally, neurohormones released by the hypothalamus and the pituitary gland (hypophysis) have received much attention owing to the unique functions of the end hormones released by their target peripheral organs (e.g., glucocorticoids released by the adrenal glands). Recent advances in mouse genetics have revealed several important metabolic functions of hypothalamic neurohormone-expressing cells, many of which are not readily explained by the action of the corresponding classical downstream hormones. Notably, the newly identified functions are better explained by the action of conventional neurotransmitters (e.g., glutamate and GABA) that constitute a neuronal circuit. In this review, we discuss the regulation of appetite and metabolism by hypothalamic neurohormone-expressing cells, with a focus on the distinct contributions of neurohormones and neurotransmitters released by these neurons.

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Disrupted hypothalamic CRH neuron responsiveness contributes to diet‐induced obesity

Cited by 19 publications

References 46 publications

Circadian Rhythms of the Hypothalamus: From Function to Physiology

Circadian Rhythms of the Hypothalamus: From Function to Physiology

Effects of Growth Hormone Receptor Ablation in Corticotropin-Releasing Hormone Cells

Neuroendocrine control of appetite and metabolism

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