Beta-aminoisobutyric acid prevents diet-induced obesity in mice with partial leptin deficiency.
Beta-Aminoisobutyric acid (BAIBA), a thymine catabolite, increases fatty acid oxidation (FAO) in liver and reduces the gain of body fat mass in Swiss (lean) mice fed a standard chow. We determined whether BAIBA could prevent obesity and related metabolic disorders in different murine models. To this end, BAIBA (100 or 500 mg/kg/day) was administered for 4 months in mice totally deficient in leptin (ob/ob). BAIBA (100 mg/kg/day) was also given for 4 months in wild-type (+/+) mice and mice partially deficient in leptin (ob/+) fed a high-calorie (HC) diet. BAIBA did not limit obesity and hepatic steatosis in ob/ob mice, but reduced liver cytolysis and inflammation. In ob/+ mice fed the HC diet, BAIBA fully prevented, or limited, the gain of body fat, steatosis and necroinflammation, glucose intolerance, and hypertriglyceridemia. Plasma beta-hydroxybutyrate was increased, whereas expression of carnitine palmitoyltransferase-1 was augmented in liver and white adipose tissue. Acetyl-CoA carboxylase was more phosphorylated, and de novo lipogenesis was less induced in liver. These favorable effects of BAIBA in ob/+ mice were associated with a restoration of plasma leptin levels. The reduction of body adiposity afforded by BAIBA was less marked in +/+ mice. Finally, BAIBA significantly stimulated the secretion of leptin in isolated ob/+ adipose cells, but not in +/+ cells. Thus, BAIBA could limit triglyceride accretion in tissues through a leptin-dependent stimulation of FAO. As partial leptin deficiency is not uncommon in the general population, supplementation with BAIBA may help to prevent diet-induced obesity and related metabolic disorders in low leptin secretors.
Begriche
Karima
K
INSERM, U773, Centre de Recherche Biomédicale Bichat Beaujon CRB3, Paris, France.
Massart
Julie
J
Abbey-Toby
Adjé
A
Igoudjil
Anissa
A
Lettéron
Philippe
P
Fromenty
Bernard
B
D000410:Alanine Transaminase / Q000097:blood / Q000378:metabolism; D000621:Aminoisobutyric Acids / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects / Q000502:physiology; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism*; D005234:Fatty Liver / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D005951:Glucose Tolerance Test; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000378:metabolism; D020738:Leptin / Q000097:blood / Q000172:deficiency* / Q000378:metabolism; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood / Q000378:metabolism
D000621:Aminoisobutyric Acids; D000975:Antioxidants; D001786:Blood Glucose; D004041:Dietary Fats; D020738:Leptin; D014280:Triglycerides; D002784:Cholesterol; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase; C033435:3-aminoisobutyric acid