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The recent discovery of pharmacological ABHD5 ligands that disrupt the interaction between ABHD5 and PLIN1 (48) demonstrate that the dissociation of ABHD5 is sufficient to stimulate adipocyte lipolysis and that these protein interactions can be targeted pharmacologically (34, 48, 49)

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Hormonal differences in fat storage and mobilization also play a role

To clarify its molecular mechanism, we performed microarray analysis in liver of Insr P1195L/ +/HFD and WT/HFD mice and found that expressions of several genes involved in BA physiology were altered

Insulin normally suppresses gluconeogenesis while promoting lipogenesis, however, under insulin resistant states such as T2D, hepatic lipogenesis remains insulin sensitive and suppression of gluconeogenesis is insulin resistant, leading to a metabolic state called selective hepatic insulin resistance (199)