Abstract
Glycogen disease type III (GSDIII), a rare incurable autosomal recessive disorder due to glycogen debranching enzyme deficiency, presents with liver, heart and skeletal muscle impairment, hepatomegaly and ketotic hypoglycemia. Muscle weakness usually worsens to fixed myopathy and cardiac involvement may present in about half of the patients during disease. Management relies on careful follow-up of symptoms and diet. No common agreement was reached on sugar restriction and treatment in adulthood. We administered two dietary regimens differing in their protein and carbohydrate content, high-protein (HPD) and high-protein/glucose-free (GFD), to our mouse model of GSDIII, starting at one month of age. Mice were monitored, either by histological, biochemical and molecular analysis and motor functional tests, until 10 months of age. GFD ameliorated muscle performance up to 10 months of age, while HPD showed little improvement only in young mice. In GFD mice, a decreased muscle glycogen content and fiber vacuolization was observed, even in aged animals indicating a protective role of proteins against skeletal muscle degeneration, at least in some districts. Hepatomegaly was reduced by about 20%. Moreover, the long-term administration of GFD did not worsen serum parameters even after eight months of high-protein diet. A decreased phosphofructokinase and pyruvate kinase activities and an increased expression of Krebs cycle and gluconeogenesis genes were seen in the liver of GFD fed mice. Our data show that the concurrent use of proteins and a strictly controlled glucose supply could reduce muscle wasting, and indicate a better metabolic control in mice with a glucose-free/high-protein diet.
| Original language | English |
|---|---|
| Pages (from-to) | 3407-3417 |
| Journal | Biochimica et Biophysica Acta - Molecular Basis of Disease |
| Volume | 1864 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2018 |
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Keywords
- Glucose-free diet
- Glycogen debranching enzyme
- Glycogen storage disease type III
- High-protein diet
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
Cite this
Glucose-free/high-protein diet improves hepatomegaly and exercise intolerance in glycogen storage disease type III mice. / Pagliarani, Serena; Lucchiari, Sabrina; Ulzi, Gianna; Ripolone, Michela; Violano, Raffaella; Fortunato, Francesco; Bordoni, Andreina; Corti, Stefania; Moggio, Maurizio; Bresolin, Nereo; Comi, Giacomo P.
In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1864, No. 10, 2018, p. 3407-3417.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Glucose-free/high-protein diet improves hepatomegaly and exercise intolerance in glycogen storage disease type III mice
AU - Pagliarani, Serena
AU - Lucchiari, Sabrina
AU - Ulzi, Gianna
AU - Ripolone, Michela
AU - Violano, Raffaella
AU - Fortunato, Francesco
AU - Bordoni, Andreina
AU - Corti, Stefania
AU - Moggio, Maurizio
AU - Bresolin, Nereo
AU - Comi, Giacomo P.
PY - 2018
Y1 - 2018
N2 - Glycogen disease type III (GSDIII), a rare incurable autosomal recessive disorder due to glycogen debranching enzyme deficiency, presents with liver, heart and skeletal muscle impairment, hepatomegaly and ketotic hypoglycemia. Muscle weakness usually worsens to fixed myopathy and cardiac involvement may present in about half of the patients during disease. Management relies on careful follow-up of symptoms and diet. No common agreement was reached on sugar restriction and treatment in adulthood. We administered two dietary regimens differing in their protein and carbohydrate content, high-protein (HPD) and high-protein/glucose-free (GFD), to our mouse model of GSDIII, starting at one month of age. Mice were monitored, either by histological, biochemical and molecular analysis and motor functional tests, until 10 months of age. GFD ameliorated muscle performance up to 10 months of age, while HPD showed little improvement only in young mice. In GFD mice, a decreased muscle glycogen content and fiber vacuolization was observed, even in aged animals indicating a protective role of proteins against skeletal muscle degeneration, at least in some districts. Hepatomegaly was reduced by about 20%. Moreover, the long-term administration of GFD did not worsen serum parameters even after eight months of high-protein diet. A decreased phosphofructokinase and pyruvate kinase activities and an increased expression of Krebs cycle and gluconeogenesis genes were seen in the liver of GFD fed mice. Our data show that the concurrent use of proteins and a strictly controlled glucose supply could reduce muscle wasting, and indicate a better metabolic control in mice with a glucose-free/high-protein diet.
AB - Glycogen disease type III (GSDIII), a rare incurable autosomal recessive disorder due to glycogen debranching enzyme deficiency, presents with liver, heart and skeletal muscle impairment, hepatomegaly and ketotic hypoglycemia. Muscle weakness usually worsens to fixed myopathy and cardiac involvement may present in about half of the patients during disease. Management relies on careful follow-up of symptoms and diet. No common agreement was reached on sugar restriction and treatment in adulthood. We administered two dietary regimens differing in their protein and carbohydrate content, high-protein (HPD) and high-protein/glucose-free (GFD), to our mouse model of GSDIII, starting at one month of age. Mice were monitored, either by histological, biochemical and molecular analysis and motor functional tests, until 10 months of age. GFD ameliorated muscle performance up to 10 months of age, while HPD showed little improvement only in young mice. In GFD mice, a decreased muscle glycogen content and fiber vacuolization was observed, even in aged animals indicating a protective role of proteins against skeletal muscle degeneration, at least in some districts. Hepatomegaly was reduced by about 20%. Moreover, the long-term administration of GFD did not worsen serum parameters even after eight months of high-protein diet. A decreased phosphofructokinase and pyruvate kinase activities and an increased expression of Krebs cycle and gluconeogenesis genes were seen in the liver of GFD fed mice. Our data show that the concurrent use of proteins and a strictly controlled glucose supply could reduce muscle wasting, and indicate a better metabolic control in mice with a glucose-free/high-protein diet.
KW - Glucose-free diet
KW - Glycogen debranching enzyme
KW - Glycogen storage disease type III
KW - High-protein diet
UR - http://www.scopus.com/inward/record.url?scp=85050946918&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85050946918&partnerID=8YFLogxK
U2 - 10.1016/j.bbadis.2018.07.031
DO - 10.1016/j.bbadis.2018.07.031
M3 - Article
AN - SCOPUS:85050946918
VL - 1864
SP - 3407
EP - 3417
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
SN - 0925-4439
IS - 10
ER -