Benefits of L-alanine or L-arginine supplementation against adiposity and glucose intolerance in monosodium glutamate-induced obesity.
OBJECTIVE
L-alanine (Ala) and L-arginine (Arg) have been reported to regulate pancreatic β-cell physiology and to prevent body fat accumulation in diet-induced obesity. Here, we assessed growth and adiposity parameters, glucose tolerance, insulin secretion and the expression of insulin and nutrient-regulated proteins in monosodium glutamate (MSG)-obese mice supplemented with either Ala or Arg.


METHODS
Male newborn C57Bl/6 mice received a daily subcutaneous injection of MSG or saline solution (CTL group), during the first 6 days of life. From 30 to 90 days of age, MSG and CTL mice received or not 2.55 % Ala (CAla or MArg groups) or 1.51 % Arg-HCl (CArg or MArg groups) in their drinking water.


RESULTS
Adult MSG mice displayed higher adiposity associated with lower phosphorylation of the adipogenic enzyme, ACC, in adipose tissue. Glucose intolerance in MSG mice was linked to lower insulin secretion and to lower expression of IRβ in adipose tissue, as well as AS160 phosphorylation in skeletal muscle. Perigonadal fat depots were smaller in Ala and Arg mice, while retroperitoneal fat pads were decreased by Ala supplementation only. Both Ala and Arg improved fed-state glycemia as well as IRβ and pAS160 content, but only Ala led to improved glucose tolerance and insulin secretion. Adipostatic signals were increased in MAla mice, as indicated by enhanced AMPK phosphorylation and pACC content in fat depots.


CONCLUSIONS
Ala supplementation led to more pronounced metabolic improvements compared to Arg, possibly due to suppression of lipogenesis through activation of the AMPK/ACC pathway.
Laboratório Integrado de Morfologia, NUPEM, Universidade Federal do Rio de Janeiro (UFRJ), Campus UFRJ-Macaé, Avenida São José do Barreto, 764, Macaé, RJ, 27965-045, Brazil.
Thiago R
TR
Araujo
Laboratório Integrado de Morfologia, NUPEM, Universidade Federal do Rio de Janeiro (UFRJ), Campus UFRJ-Macaé, Avenida São José do Barreto, 764, Macaé, RJ, 27965-045, Brazil.
Israelle N
IN
Freitas
Laboratório de Pâncreas Endócrino e Metabolismo, Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.
Jean F
JF
Vettorazzi
Laboratório de Pâncreas Endócrino e Metabolismo, Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.
Thiago M
TM
Batista
Laboratório de Pâncreas Endócrino e Metabolismo, Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.
Junia C
JC
Santos-Silva
Laboratório de Fisiologia Endócrina e Metabolismo, Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná (UNIOESTE), Cascavel, PR, Brazil.
Maria L
ML
Bonfleur
Laboratório de Fisiologia Endócrina e Metabolismo, Centro de Ciências Biológicas e da Saúde, Universidade Estadual do Oeste do Paraná (UNIOESTE), Cascavel, PR, Brazil.
Sandra L
SL
Balbo
Laboratório de Pâncreas Endócrino e Metabolismo, Departamento de Biologia Estrutural e Funcional, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil.
Antonio C
AC
Boschero
Laboratório Integrado de Morfologia, NUPEM, Universidade Federal do Rio de Janeiro (UFRJ), Campus UFRJ-Macaé, Avenida São José do Barreto, 764, Macaé, RJ, 27965-045, Brazil.
Everardo M
EM
Carneiro
Laboratório Integrado de Morfologia, NUPEM, Universidade Federal do Rio de Janeiro (UFRJ), Campus UFRJ-Macaé, Avenida São José do Barreto, 764, Macaé, RJ, 27965-045, Brazil. rosaneribeirobio@gmail.com.
Rosane A
RA
Ribeiro
D050154:Adiposity / Q000187:drug effects*; D000409:Alanine / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D019587:Dietary Supplements; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D018149:Glucose Intolerance / Q000188:drug therapy*; D006706:Homeostasis / Q000187:drug effects; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000139:chemically induced / Q000188:drug therapy*; D010766:Phosphorylation; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D012970:Sodium Glutamate; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D020690:GTPase-Activating Proteins; D007328:Insulin; D012709:Serum Albumin; C505647:Tbc1d4 protein, mouse; D014280:Triglycerides; D001120:Arginine; D002784:Cholesterol; D011972:Receptor, Insulin; D000409:Alanine; D012970:Sodium Glutamate
AMP-activated kinase; Insulin secretion; L-alanine supplementation; L-arginine supplementation; MSG obesity; Neuroendocrine disorder