The Statin Target Hmgcr Regulates Energy Metabolism and Food Intake through Central Mechanisms

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Williams, Michael J.Uppsala universitet,Schiöth: Funktionell farmakologi (author)

The Statin Target Hmgcr Regulates Energy Metabolism and Food Intake through Central Mechanisms

Article/chapterEnglish2022

Publisher, publication year, extent ...

2022-03-11
MDPI,2022
electronicrdacarrier

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LIBRIS-ID:oai:DiVA.org:uu-472876
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-472876URI
https://doi.org/10.3390/cells11060970DOI
https://res.slu.se/id/publ/116721URI

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Language:English
Summary in:English

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SwePubSwePub

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

The statin drug target, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), is strongly linked to body mass index (BMI), yet how HMGCR influences BMI is not understood. In mammals, studies of peripheral HMGCR have not clearly identified a role in BMI maintenance and, despite considerable central nervous system expression, a function for central HMGCR has not been determined. Similar to mammals, Hmgcr is highly expressed in the Drosophila melanogaster brain. Therefore, genetic and pharmacological studies were performed to identify how central Hmgcr regulates Drosophila energy metabolism and feeding behavior. We found that inhibiting Hmgcr, in insulin-producing cells of the Drosophila pars intercerebralis (PI), the fly hypothalamic equivalent, significantly reduces the expression of insulin-like peptides, severely decreasing insulin signaling. In fact, reducing Hmgcr expression throughout development causes decreased body size, increased lipid storage, hyperglycemia, and hyperphagia. Furthermore, the Hmgcr induced hyperphagia phenotype requires a conserved insulin-regulated alpha-glucosidase, target of brain insulin (tobi). In rats and mice, acute inhibition of hypothalamic Hmgcr activity stimulates food intake. This study presents evidence of how central Hmgcr regulation of metabolism and food intake could influence BMI.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
NATURVETENSKAP Biologi Cellbiologi hsv//swe
NATURAL SCIENCES Biological Sciences Cell Biology hsv//eng
body maintenance index
obesity
statins
mevalonate pathway
metabolism
feeding behavior
hypothalamus

Added entries (persons, corporate bodies, meetings, titles ...)

Alsehli, Ahmed M.Uppsala universitet,Schiöth: Funktionell farmakologi,King Abdulaziz Univ & Hosp, Fac Med, Al Ehtifalat St, Jeddah 21589, Saudi Arabia.(Swepub:uu)ahmal312 (author)
Gartner, Sarah N.Univ Waikato, Dept Biol Sci, Private Bag 3105, Hamilton 3240, New Zealand. (author)
Clemensson, Laura EmilyUppsala universitet,Schiöth: Funktionell farmakologi(Swepub:uu)laucl164 (author)
Liao, SifangUppsala universitet,Schiöth: Funktionell farmakologi(Swepub:uu)sifli166 (author)
Eriksson, AndersUppsala universitet,Schiöth: Funktionell farmakologi (author)
Isgrove, KirianaUniv Waikato, Dept Biol Sci, Private Bag 3105, Hamilton 3240, New Zealand. (author)
Thelander, LinaUppsala universitet,Schiöth: Funktionell farmakologi (author)
Khan, ZaidSwedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Uppsala universitet,Schiöth: Funktionell farmakologi,Swedish Univ Agr Sci SLU, Dept Plant Protect Biol, Sundsvagen 14, S-23053 Alnarp, Sweden.,Växtskyddsbiologi,Department of Plant Protection Biology,Uppsala University (author)
Itskov, Pavel M.Uppsala universitet,Schiöth: Funktionell farmakologi(Swepub:uu)pavit568 (author)
Moulin, ThiagoUppsala universitet,Schiöth: Funktionell farmakologi(Swepub:uu)thima875 (author)
Ambrosi, ValerieUppsala universitet,Schiöth: Funktionell farmakologi (author)
Al-Sabri, Mohamed H.Uppsala universitet,Schiöth: Funktionell farmakologi(Swepub:uu)mohal518 (author)
Lagunas-Rangel, Francisco AlejandroUppsala universitet,Schiöth: Funktionell farmakologi(Swepub:uu)frala489 (author)
Olszewski, Pawel K.Univ Waikato, Dept Biol Sci, Private Bag 3105, Hamilton 3240, New Zealand. (author)
Schiöth, Helgi B.Uppsala universitet,Schiöth: Funktionell farmakologi(Swepub:uu)helgschi (author)
Uppsala universitetSchiöth: Funktionell farmakologi (creator_code:org_t)
Sveriges lantbruksuniversitet

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In:Cells: MDPI11:62073-4409

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Endocrinology an ...

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