Chronic sympathoexcitation through loss of Vav3, a Rac1 activator, results in divergent effects on metabolic syndrome and obesity depending on diet

Cell Metab. 2013 Aug 6;18(2):199-211. doi: 10.1016/j.cmet.2013.07.001.


The role of the sympathetic nervous system, stress, and hypertension in metabolic syndrome and obesity remains unclear. To clarify this issue, we utilized genetically engineered mice showing chronic sympathoexcitation and hypertension due to lack of Vav3, a Rac1 activator. Here, we report that these animals develop metabolic syndrome under chow diet. However, they show protection from metabolic syndrome and obesity under fatty diets. These effects are elicited by α1-adrenergic- and diet-dependent metabolic changes in liver and the α1/β3 adrenergic-mediated stimulation of brown adipocyte thermogenesis. These responses seem to be engaged by the local action of noradrenaline in target tissues rather than by long-range effects of adrenaline. By contrast, they are not triggered by low parasympathetic drive or the hypertensive state present in Vav3-deficient mice. These results indicate that the sympathetic system plays divergent roles in the etiology of metabolic diseases depending on food regimen, sympathoexcitation source, and disease stage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes, Brown / metabolism
  • Animals
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / metabolism
  • Diet
  • Diet, High-Fat / adverse effects
  • Energy Metabolism / genetics
  • Epinephrine / metabolism
  • Fatty Acids / metabolism*
  • Fatty Liver / genetics
  • Fatty Liver / metabolism
  • Hypertension / genetics
  • Hypertension / metabolism
  • Liver / metabolism
  • Metabolic Syndrome / genetics
  • Metabolic Syndrome / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neuropeptides / metabolism
  • Norepinephrine / metabolism
  • Obesity / genetics
  • Obesity / metabolism*
  • Proto-Oncogene Proteins c-vav / deficiency
  • Proto-Oncogene Proteins c-vav / genetics*
  • Sympathetic Nervous System / metabolism*
  • Thermogenesis / genetics
  • rac1 GTP-Binding Protein / metabolism


  • Fatty Acids
  • Neuropeptides
  • Proto-Oncogene Proteins c-vav
  • Rac1 protein, mouse
  • Vav3 protein, mouse
  • rac1 GTP-Binding Protein
  • Norepinephrine
  • Epinephrine