Loss of function of mammalian RIIβ, a regulatory subunit of PKA expressed in brain and adipose tissue, results in mice that are lean and insulin sensitive.
In addition, based on the findings from fetuin-A deficient mice that remain lean and insulin sensitive fed a high-fat diet [8], fetuin-A may have long-term effects on energy expenditure and lipid oxidation, independent of the aforementioned mechanisms.
Despite this mitochondria stress, the mice remain lean and insulin sensitive even at 10 months of age.
There was an increase in adiponectin levels and a reduction in leptin expression in the WAT of FSP27-deficient mice, which is consistent with their lean and insulin sensitive phenotypes.
Two perilipins have been characterized in flies [ 29]: Lsd-2 promotes fat storage as mutants of Lsd-2 are lean and starvation sensitive [ 30]; and perilipin-1 mutants display adult onset obesity and hyperphagia [ 31], suggesting a role for this molecule in controlled access of the lipid droplets to lipolytic enzymes.
Indeed, although complete lack of Socs-3 is embryonic lethal, mice with only one functional copy of Socs-3 or those with neuronal deletion of Socs-3 are lean and leptin sensitive (Howard et al., 2004; Kievit et al., 2006; Mori et al., 2004).
We have found that deletion of Ghsr gene enhances BAT thermogenesis in aged mice, resulting in a lean and insulin-sensitive phenotype [ 34].
Taken together, the results of the present study indicate that deletion or reduction of BACE1 not only renders mice lean and insulin-sensitive when fed on a regular chow diet, but also causes them to be, at least partially, protected against the metabolic derangement caused by chronic exposure to nutrient excess, in the form of an HFD.
Shc-deficient mice (ShcKO) were previously shown to be lean, insulin sensitive, and resistant to high-fat diet and obesity.
