Vidal-Puig noted that abnormal production of adipocytokines with increases in adipose tissue inflammation remains possible with the adipose tissue expandability hypothesis and that as 70% of fat delivered to the liver is not viscerally derived. Failure of subcutaneous adipose tissue to expand would also be predicted to lead to insulin resistance. Adipose tissue expandability implies the existence of metabolic set points. Once individuals reach their maximal adipose tissue mass, metabolic complications ensue, suggesting that pharmacological agents increasing adipose tissue expandability would be beneficial, allowing treatment of NASH, diabetes, and dyslipidemia. Identification of organ-specific lipid networks may provide key information for specific treatments, and specific lipotoxicity patterns may be useful as biomarkers of CVD and metabolic risk.

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