However, severe reduction of PPARγ by treatment of heterozygous PPARγ-deficient mice with a RXR antagonist or a PPAR antagonist depletes white adipose tissue and markedly decreases leptin and adiponectin levels and energy dissipation, which increases TG content in skeletal muscle and liver, thereby leading to the re-emergence of insulin resistance [53]. Here, LEP is linked to Insulin resistance.