Hypothalamic hormone-sensitive lipase regulates appetite and energy homeostasis

Research output: Contribution to journal › Journal article › Research › peer-review

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Hypothalamic hormone-sensitive lipase regulates appetite and energy homeostasis. / Hundahl, Cecilie; Kotzbeck, Petra; Burm, Hayley Beth; Christiansen, Søren H; Torz, Lola; Helge, Aske Wulff; Madsen, Martin Peter; Ratner, Cecilia; Serup, Annette K; Thompson, Jonatan J.; Eichmann, Thomas O; Pers, Tune H; Woldbye, David P; Piomelli, Daniele; Kiens, Bente; Zechner, Rudolf; Skov, Louise Julie; Holst, Birgitte.

In: Molecular Metabolism, Vol. 47, 101174, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Hundahl, C, Kotzbeck, P, Burm, HB, Christiansen, SH, Torz, L, Helge, AW, Madsen, MP, Ratner, C, Serup, AK, Thompson, JJ, Eichmann, TO, Pers, TH, Woldbye, DP, Piomelli, D, Kiens, B, Zechner, R, Skov, LJ & Holst, B 2021, 'Hypothalamic hormone-sensitive lipase regulates appetite and energy homeostasis', Molecular Metabolism, vol. 47, 101174. https://doi.org/10.1016/j.molmet.2021.101174

APA

Hundahl, C., Kotzbeck, P., Burm, H. B., Christiansen, S. H., Torz, L., Helge, A. W., Madsen, M. P., Ratner, C., Serup, A. K., Thompson, J. J., Eichmann, T. O., Pers, T. H., Woldbye, D. P., Piomelli, D., Kiens, B., Zechner, R., Skov, L. J., & Holst, B. (2021). Hypothalamic hormone-sensitive lipase regulates appetite and energy homeostasis. Molecular Metabolism, 47, [101174]. https://doi.org/10.1016/j.molmet.2021.101174

Vancouver

Hundahl C, Kotzbeck P, Burm HB, Christiansen SH, Torz L, Helge AW et al. Hypothalamic hormone-sensitive lipase regulates appetite and energy homeostasis. Molecular Metabolism. 2021;47. 101174. https://doi.org/10.1016/j.molmet.2021.101174

Author

Hundahl, Cecilie ; Kotzbeck, Petra ; Burm, Hayley Beth ; Christiansen, Søren H ; Torz, Lola ; Helge, Aske Wulff ; Madsen, Martin Peter ; Ratner, Cecilia ; Serup, Annette K ; Thompson, Jonatan J. ; Eichmann, Thomas O ; Pers, Tune H ; Woldbye, David P ; Piomelli, Daniele ; Kiens, Bente ; Zechner, Rudolf ; Skov, Louise Julie ; Holst, Birgitte. / Hypothalamic hormone-sensitive lipase regulates appetite and energy homeostasis. In: Molecular Metabolism. 2021 ; Vol. 47.

Bibtex

@article{06bc7f4498c548d793dc62e75823becb,

title = "Hypothalamic hormone-sensitive lipase regulates appetite and energy homeostasis",

abstract = "Objective: To investigate the importance of central Hormone-Sensitive Lipase (HSL) expression in the regulation of food intake and body weight in mice in order to clarify whether intracellular lipolysis in the mammalian hypothalamus plays a role in regulating appetite.Methods: Using pharmacological and genetic approaches, we investigated the role of HSL in the rodent brain in the regulation of feeding and energy homeostasis, under basal conditions, during acute stress and high-fat diet feeding.Results: We find that HSL, a key enzyme in the catabolism of cellular lipid stores, is expressed in the appetite-regulating centers of the hypothalamus and is activated by acute stress through a mechanism similar to that observed in adipose tissue and skeletal muscle. Inhibition of HSL in rodent models by a synthetic ligand, global knockout or brain-specific deletion of HSL prevents the decrease in food intake normally seen in response to acute stress and is associated with increased expression of the orexigenic peptides neuropeptide Y (NPY) and Agouti-related peptide (AgRP). The increased food intake can be reversed by adeno-associated virus-mediated reintroduction of HSL in neurons of the mediobasal hypothalamus. Importantly, metabolic stress induced by a high-fat diet also enhances the hyperphagic phenotype of HSL-deficient mice. Specific deletion of HSL in the ventromedial hypothalamic nucleus (VMH) or AgRP neurons reveals that HSL in the VMH plays a role in both acute stress-induced food intake and high-fat diet-induced obesity.Conclusions: Our results indicate that HSL activity in the mediobasal hypothalamus is involved in the acute reduction in food intake during the acute stress response and in the sensing of high-fat diet.",

keywords = "Faculty of Science, Appetite regulation, Stress, Obesity, Hypothalamus",

author = "Cecilie Hundahl and Petra Kotzbeck and Burm, {Hayley Beth} and Christiansen, {S{\o}ren H} and Lola Torz and Helge, {Aske Wulff} and Madsen, {Martin Peter} and Cecilia Ratner and Serup, {Annette K} and Thompson, {Jonatan J.} and Eichmann, {Thomas O} and Pers, {Tune H} and Woldbye, {David P} and Daniele Piomelli and Bente Kiens and Rudolf Zechner and Skov, {Louise Julie} and Birgitte Holst",

note = "CURIS 2021 NEXS 076",

year = "2021",

doi = "10.1016/j.molmet.2021.101174",

language = "English",

volume = "47",

journal = "Molecular Metabolism",

issn = "2212-8778",

publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Hypothalamic hormone-sensitive lipase regulates appetite and energy homeostasis

AU - Hundahl, Cecilie

AU - Kotzbeck, Petra

AU - Burm, Hayley Beth

AU - Christiansen, Søren H

AU - Torz, Lola

AU - Helge, Aske Wulff

AU - Madsen, Martin Peter

AU - Ratner, Cecilia

AU - Serup, Annette K

AU - Thompson, Jonatan J.

AU - Eichmann, Thomas O

AU - Pers, Tune H

AU - Woldbye, David P

AU - Piomelli, Daniele

AU - Kiens, Bente

AU - Zechner, Rudolf

AU - Skov, Louise Julie

AU - Holst, Birgitte

N1 - CURIS 2021 NEXS 076

PY - 2021

Y1 - 2021

N2 - Objective: To investigate the importance of central Hormone-Sensitive Lipase (HSL) expression in the regulation of food intake and body weight in mice in order to clarify whether intracellular lipolysis in the mammalian hypothalamus plays a role in regulating appetite.Methods: Using pharmacological and genetic approaches, we investigated the role of HSL in the rodent brain in the regulation of feeding and energy homeostasis, under basal conditions, during acute stress and high-fat diet feeding.Results: We find that HSL, a key enzyme in the catabolism of cellular lipid stores, is expressed in the appetite-regulating centers of the hypothalamus and is activated by acute stress through a mechanism similar to that observed in adipose tissue and skeletal muscle. Inhibition of HSL in rodent models by a synthetic ligand, global knockout or brain-specific deletion of HSL prevents the decrease in food intake normally seen in response to acute stress and is associated with increased expression of the orexigenic peptides neuropeptide Y (NPY) and Agouti-related peptide (AgRP). The increased food intake can be reversed by adeno-associated virus-mediated reintroduction of HSL in neurons of the mediobasal hypothalamus. Importantly, metabolic stress induced by a high-fat diet also enhances the hyperphagic phenotype of HSL-deficient mice. Specific deletion of HSL in the ventromedial hypothalamic nucleus (VMH) or AgRP neurons reveals that HSL in the VMH plays a role in both acute stress-induced food intake and high-fat diet-induced obesity.Conclusions: Our results indicate that HSL activity in the mediobasal hypothalamus is involved in the acute reduction in food intake during the acute stress response and in the sensing of high-fat diet.

AB - Objective: To investigate the importance of central Hormone-Sensitive Lipase (HSL) expression in the regulation of food intake and body weight in mice in order to clarify whether intracellular lipolysis in the mammalian hypothalamus plays a role in regulating appetite.Methods: Using pharmacological and genetic approaches, we investigated the role of HSL in the rodent brain in the regulation of feeding and energy homeostasis, under basal conditions, during acute stress and high-fat diet feeding.Results: We find that HSL, a key enzyme in the catabolism of cellular lipid stores, is expressed in the appetite-regulating centers of the hypothalamus and is activated by acute stress through a mechanism similar to that observed in adipose tissue and skeletal muscle. Inhibition of HSL in rodent models by a synthetic ligand, global knockout or brain-specific deletion of HSL prevents the decrease in food intake normally seen in response to acute stress and is associated with increased expression of the orexigenic peptides neuropeptide Y (NPY) and Agouti-related peptide (AgRP). The increased food intake can be reversed by adeno-associated virus-mediated reintroduction of HSL in neurons of the mediobasal hypothalamus. Importantly, metabolic stress induced by a high-fat diet also enhances the hyperphagic phenotype of HSL-deficient mice. Specific deletion of HSL in the ventromedial hypothalamic nucleus (VMH) or AgRP neurons reveals that HSL in the VMH plays a role in both acute stress-induced food intake and high-fat diet-induced obesity.Conclusions: Our results indicate that HSL activity in the mediobasal hypothalamus is involved in the acute reduction in food intake during the acute stress response and in the sensing of high-fat diet.

KW - Faculty of Science

KW - Appetite regulation

KW - Stress

KW - Obesity

KW - Hypothalamus

U2 - 10.1016/j.molmet.2021.101174

DO - 10.1016/j.molmet.2021.101174

M3 - Journal article

C2 - 33549847

VL - 47

JO - Molecular Metabolism

JF - Molecular Metabolism

SN - 2212-8778

M1 - 101174

ER -

ID: 256632296