Peripherally administered melanocortins induce mice fat browning and prevent obesity

Background/objectives The browning of white adipose tissue (WAT) has been in the spotlight during the last years, becoming an attractive approach to combat obesity. Melanocortin neuropeptides, such as α-melanocyte-stimulating hormone (α-MSH), are well-known regulators of appetite at the central nerv...

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Published inInternational Journal of Obesity Vol. 43; no. 5; pp. 1058 - 1069
Main Authors Rodrigues, Adriana R., Salazar, Maria J., Rocha-Rodrigues, Sílvia, Gonçalves, Inês O., Cruz, Célia, Neves, Delminda, Almeida, Henrique, Magalhães, José, Gouveia, Alexandra M.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 01.05.2019
Nature Publishing Group
Subjects
13/51
14/63
3T3-L1 Cells
64/60
692/163/2743/393
692/699/2743/393
82/29
Adipocytes
Adipocytes - drug effects
Adipocytes - metabolism
Adipose tissue
Adipose tissue (brown)
Adipose Tissue, Beige - drug effects
Adipose Tissue, Beige - metabolism
Adipose Tissue, Brown - drug effects
Adipose Tissue, Brown - metabolism
Adipose Tissue, White - drug effects
Adipose Tissue, White - metabolism
Animals
Appetite
Biosynthesis
Body fat
Body weight
Browning
Cells, Cultured
Central nervous system
Diet
Diet, High-Fat
Epidemiology
Food intake
Gene expression
Glucose
Health aspects
Health Promotion and Disease Prevention
Homeostasis
Hormones
Insulin
Insulin resistance
Internal Medicine
Laboratory rats
Lipids
Medicine
Medicine & Public Health
Melanocortin
Melanocortins - pharmacology
Melanocyte stimulating hormone
Metabolic Diseases
Mice
Mice, Inbred C57BL
Mitochondria
Neuropeptides
Obesity
Obesity - metabolism
Obesity - prevention & control
Oxygen consumption
Phenotypes
Prevention
Public Health
Regulators
Respiration
Respiratory rate
Thermogenesis - drug effects
Thermogenesis - physiology
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Abstract Background/objectives The browning of white adipose tissue (WAT) has been in the spotlight during the last years, becoming an attractive approach to combat obesity. Melanocortin neuropeptides, such as α-melanocyte-stimulating hormone (α-MSH), are well-known regulators of appetite at the central nervous system, but its role in adipocyte metabolism is poorly elucidated. This study sought to verify if α-MSH can induce transdifferentiation of white to brown/beige adipocytes and to determine whether it can ameliorate the obesity phenotype. Methods The browning effect of α-MSH was determined in isolated adipocytes using the 3T3-L1 cell line and in inguinal subcutaneous adipose tissue (ingWAT) of diet-induced obese (DIO) mice by quantifying the expression of browning hallmark genes, oxygen consumption, and mitochondrial biogenesis. α-MSH protection from diet-induced obesity was evaluated by analyzing mice body weight, fat mass, and lipid and glucose serum profiles. Results Here, we report that α-MSH activates a thermogenic gene program and increases the mitochondrial respiratory rate in 3T3-L1 adipocytes and ingWAT of DIO mice. Without affecting food intake, peripheral administration of α-MSH decreases body weight and ingWAT mass, promoting a significant rise in the number of smaller adipocytes, whereas it lowered the larger ones. Additionally, there was an increase in the mass of brown adipose tissue. Browning activation occurs concomitantly with improvement on serum lipid profile, insulin resistance, and glucose homeostasis. Conclusions This study highlights the anti-obesity properties of melanocortins by promoting ingWAT browning and provides new perspectives for future designing of more effective therapeutic strategies.
AbstractList The browning of white adipose tissue (WAT) has been in the spotlight during the last years, becoming an attractive approach to combat obesity. Melanocortin neuropeptides, such as α-melanocyte-stimulating hormone (α-MSH), are well-known regulators of appetite at the central nervous system, but its role in adipocyte metabolism is poorly elucidated. This study sought to verify if α-MSH can induce transdifferentiation of white to brown/beige adipocytes and to determine whether it can ameliorate the obesity phenotype. The browning effect of α-MSH was determined in isolated adipocytes using the 3T3-L1 cell line and in inguinal subcutaneous adipose tissue (ingWAT) of diet-induced obese (DIO) mice by quantifying the expression of browning hallmark genes, oxygen consumption, and mitochondrial biogenesis. α-MSH protection from diet-induced obesity was evaluated by analyzing mice body weight, fat mass, and lipid and glucose serum profiles. Here, we report that α-MSH activates a thermogenic gene program and increases the mitochondrial respiratory rate in 3T3-L1 adipocytes and ingWAT of DIO mice. Without affecting food intake, peripheral administration of α-MSH decreases body weight and ingWAT mass, promoting a significant rise in the number of smaller adipocytes, whereas it lowered the larger ones. Additionally, there was an increase in the mass of brown adipose tissue. Browning activation occurs concomitantly with improvement on serum lipid profile, insulin resistance, and glucose homeostasis. This study highlights the anti-obesity properties of melanocortins by promoting ingWAT browning and provides new perspectives for future designing of more effective therapeutic strategies.
Background/objectives The browning of white adipose tissue (WAT) has been in the spotlight during the last years, becoming an attractive approach to combat obesity. Melanocortin neuropeptides, such as [alpha]-melanocyte-stimulating hormone ([alpha]-MSH), are well-known regulators of appetite at the central nervous system, but its role in adipocyte metabolism is poorly elucidated. This study sought to verify if [alpha]-MSH can induce transdifferentiation of white to brown/beige adipocytes and to determine whether it can ameliorate the obesity phenotype. Methods The browning effect of [alpha]-MSH was determined in isolated adipocytes using the 3T3-L1 cell line and in inguinal subcutaneous adipose tissue (ingWAT) of diet-induced obese (DIO) mice by quantifying the expression of browning hallmark genes, oxygen consumption, and mitochondrial biogenesis. [alpha]-MSH protection from diet-induced obesity was evaluated by analyzing mice body weight, fat mass, and lipid and glucose serum profiles. Results Here, we report that [alpha]-MSH activates a thermogenic gene program and increases the mitochondrial respiratory rate in 3T3-L1 adipocytes and ingWAT of DIO mice. Without affecting food intake, peripheral administration of [alpha]-MSH decreases body weight and ingWAT mass, promoting a significant rise in the number of smaller adipocytes, whereas it lowered the larger ones. Additionally, there was an increase in the mass of brown adipose tissue. Browning activation occurs concomitantly with improvement on serum lipid profile, insulin resistance, and glucose homeostasis. Conclusions This study highlights the anti-obesity properties of melanocortins by promoting ingWAT browning and provides new perspectives for future designing of more effective therapeutic strategies.
Background/objectives The browning of white adipose tissue (WAT) has been in the spotlight during the last years, becoming an attractive approach to combat obesity. Melanocortin neuropeptides, such as α-melanocyte-stimulating hormone (α-MSH), are well-known regulators of appetite at the central nervous system, but its role in adipocyte metabolism is poorly elucidated. This study sought to verify if α-MSH can induce transdifferentiation of white to brown/beige adipocytes and to determine whether it can ameliorate the obesity phenotype. Methods The browning effect of α-MSH was determined in isolated adipocytes using the 3T3-L1 cell line and in inguinal subcutaneous adipose tissue (ingWAT) of diet-induced obese (DIO) mice by quantifying the expression of browning hallmark genes, oxygen consumption, and mitochondrial biogenesis. α-MSH protection from diet-induced obesity was evaluated by analyzing mice body weight, fat mass, and lipid and glucose serum profiles. Results Here, we report that α-MSH activates a thermogenic gene program and increases the mitochondrial respiratory rate in 3T3-L1 adipocytes and ingWAT of DIO mice. Without affecting food intake, peripheral administration of α-MSH decreases body weight and ingWAT mass, promoting a significant rise in the number of smaller adipocytes, whereas it lowered the larger ones. Additionally, there was an increase in the mass of brown adipose tissue. Browning activation occurs concomitantly with improvement on serum lipid profile, insulin resistance, and glucose homeostasis. Conclusions This study highlights the anti-obesity properties of melanocortins by promoting ingWAT browning and provides new perspectives for future designing of more effective therapeutic strategies.
The browning of white adipose tissue (WAT) has been in the spotlight during the last years, becoming an attractive approach to combat obesity. Melanocortin neuropeptides, such as [alpha]-melanocyte-stimulating hormone ([alpha]-MSH), are well-known regulators of appetite at the central nervous system, but its role in adipocyte metabolism is poorly elucidated. This study sought to verify if [alpha]-MSH can induce transdifferentiation of white to brown/beige adipocytes and to determine whether it can ameliorate the obesity phenotype. The browning effect of [alpha]-MSH was determined in isolated adipocytes using the 3T3-L1 cell line and in inguinal subcutaneous adipose tissue (ingWAT) of diet-induced obese (DIO) mice by quantifying the expression of browning hallmark genes, oxygen consumption, and mitochondrial biogenesis. [alpha]-MSH protection from diet-induced obesity was evaluated by analyzing mice body weight, fat mass, and lipid and glucose serum profiles. Here, we report that [alpha]-MSH activates a thermogenic gene program and increases the mitochondrial respiratory rate in 3T3-L1 adipocytes and ingWAT of DIO mice. Without affecting food intake, peripheral administration of [alpha]-MSH decreases body weight and ingWAT mass, promoting a significant rise in the number of smaller adipocytes, whereas it lowered the larger ones. Additionally, there was an increase in the mass of brown adipose tissue. Browning activation occurs concomitantly with improvement on serum lipid profile, insulin resistance, and glucose homeostasis. This study highlights the anti-obesity properties of melanocortins by promoting ingWAT browning and provides new perspectives for future designing of more effective therapeutic strategies.
Background/objectivesThe browning of white adipose tissue (WAT) has been in the spotlight during the last years, becoming an attractive approach to combat obesity. Melanocortin neuropeptides, such as α-melanocyte-stimulating hormone (α-MSH), are well-known regulators of appetite at the central nervous system, but its role in adipocyte metabolism is poorly elucidated. This study sought to verify if α-MSH can induce transdifferentiation of white to brown/beige adipocytes and to determine whether it can ameliorate the obesity phenotype.MethodsThe browning effect of α-MSH was determined in isolated adipocytes using the 3T3-L1 cell line and in inguinal subcutaneous adipose tissue (ingWAT) of diet-induced obese (DIO) mice by quantifying the expression of browning hallmark genes, oxygen consumption, and mitochondrial biogenesis. α-MSH protection from diet-induced obesity was evaluated by analyzing mice body weight, fat mass, and lipid and glucose serum profiles.ResultsHere, we report that α-MSH activates a thermogenic gene program and increases the mitochondrial respiratory rate in 3T3-L1 adipocytes and ingWAT of DIO mice. Without affecting food intake, peripheral administration of α-MSH decreases body weight and ingWAT mass, promoting a significant rise in the number of smaller adipocytes, whereas it lowered the larger ones. Additionally, there was an increase in the mass of brown adipose tissue. Browning activation occurs concomitantly with improvement on serum lipid profile, insulin resistance, and glucose homeostasis.ConclusionsThis study highlights the anti-obesity properties of melanocortins by promoting ingWAT browning and provides new perspectives for future designing of more effective therapeutic strategies.
Audience Academic
Author Salazar, Maria J.
Rodrigues, Adriana R.
Neves, Delminda
Rocha-Rodrigues, Sílvia
Almeida, Henrique
Cruz, Célia
Magalhães, José
Gonçalves, Inês O.
Gouveia, Alexandra M.
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  givenname: Maria J.
  surname: Salazar
  fullname: Salazar, Maria J.
  organization: Departamento de Biomedicina – Unidade de Biologia Experimental, Faculdade de Medicina do Porto; IBMC – Instituto de Biologia Molecular e Celular and I3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto
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  givenname: Sílvia
  surname: Rocha-Rodrigues
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  surname: Magalhães
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  orcidid: 0000-0001-8784-4246
  surname: Gouveia
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  email: agouveia@med.up.pt
  organization: Departamento de Biomedicina – Unidade de Biologia Experimental, Faculdade de Medicina do Porto; IBMC – Instituto de Biologia Molecular e Celular and I3S – Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Faculdade de Ciências da Nutrição e Alimentação, Universidade do Porto
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PublicationPlace_xml – name: London
– name: England
PublicationSubtitle Official journal of the International Association for the Study of Obesity
PublicationTitle International Journal of Obesity
PublicationTitleAbbrev Int J Obes
PublicationTitleAlternate Int J Obes (Lond)
PublicationYear 2019
Publisher Nature Publishing Group UK
Nature Publishing Group
Publisher_xml – name: Nature Publishing Group UK
– name: Nature Publishing Group
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Snippet Background/objectives The browning of white adipose tissue (WAT) has been in the spotlight during the last years, becoming an attractive approach to combat...
The browning of white adipose tissue (WAT) has been in the spotlight during the last years, becoming an attractive approach to combat obesity. Melanocortin...
Background/objectives The browning of white adipose tissue (WAT) has been in the spotlight during the last years, becoming an attractive approach to combat...
Background/objectivesThe browning of white adipose tissue (WAT) has been in the spotlight during the last years, becoming an attractive approach to combat...
BACKGROUND/OBJECTIVESThe browning of white adipose tissue (WAT) has been in the spotlight during the last years, becoming an attractive approach to combat...
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gale
crossref
pubmed
springer
SourceType Aggregation Database
Index Database
Publisher
StartPage 1058
SubjectTerms 13/51
14/63
3T3-L1 Cells
64/60
692/163/2743/393
692/699/2743/393
82/29
Adipocytes
Adipocytes - drug effects
Adipocytes - metabolism
Adipose tissue
Adipose tissue (brown)
Adipose Tissue, Beige - drug effects
Adipose Tissue, Beige - metabolism
Adipose Tissue, Brown - drug effects
Adipose Tissue, Brown - metabolism
Adipose Tissue, White - drug effects
Adipose Tissue, White - metabolism
Animals
Appetite
Biosynthesis
Body fat
Body weight
Browning
Cells, Cultured
Central nervous system
Diet
Diet, High-Fat
Epidemiology
Food intake
Gene expression
Glucose
Health aspects
Health Promotion and Disease Prevention
Homeostasis
Hormones
Insulin
Insulin resistance
Internal Medicine
Laboratory rats
Lipids
Medicine
Medicine & Public Health
Melanocortin
Melanocortins - pharmacology
Melanocyte stimulating hormone
Metabolic Diseases
Mice
Mice, Inbred C57BL
Mitochondria
Neuropeptides
Obesity
Obesity - metabolism
Obesity - prevention & control
Oxygen consumption
Phenotypes
Prevention
Public Health
Regulators
Respiration
Respiratory rate
Thermogenesis - drug effects
Thermogenesis - physiology
Title Peripherally administered melanocortins induce mice fat browning and prevent obesity
URI https://link.springer.com/article/10.1038/s41366-018-0155-5
https://www.ncbi.nlm.nih.gov/pubmed/30018312
https://www.proquest.com/docview/2221218649
https://search.proquest.com/docview/2071574414
Volume 43
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