Effects of β-aminoisobutyric acid on leptin production and lipid homeostasis: mechanisms and possible relevance for the prevention of obesity.
Beta-aminoisobutyric acid (BAIBA) is a catabolite of thymine and antiretroviral thymine analogues AZT and d4T. We recently discovered that this beta-amino acid is able to enhance fatty acid oxidation and reduce body weight in mice through an increased production of leptin by the white adipose tissue (WAT). Furthermore, BAIBA could have favourable effects on nonalcoholic steatohepatitis in a leptin-independent manner. In the present review, we shall recall the circumstances that led us to discover the effects of BAIBA on body fat mass and lipid homeostasis. In addition, we put forward several hypothetical mechanisms whereby BAIBA could enhance leptin secretion by WAT and present some anti-inflammatory effects in the liver. We also discuss in this review (i) the deleterious impacts caused by the absence of, or low leptin expression on lipid homeostasis and body weight in humans and animals and (ii) recent data from other investigators suggesting that increasing leptin levels and/or responsiveness may be indeed an attractive pharmacological strategy in order to prevent (and/or treat) obesity, at least in some individuals.
Begriche
Karima
K
INSERM, U620, Université de Rennes 1, Rennes, France.
Massart
Julie
J
Fromenty
Bernard
B
D000621:Aminoisobutyric Acids / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D020738:Leptin / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*
D000621:Aminoisobutyric Acids; D020738:Leptin; C033435:3-aminoisobutyric acid