Enhancing endogenous levels of GLP1 dampens acute olanzapine induced perturbations in lipid and glucose metabolism.

Olanzapine is a second-generation antipsychotic (SGA) used in the treatment of schizophrenia and several on- and off-label conditions. While effective in reducing psychoses, acute olanzapine treatment causes rapid hyperglycemia, insulin resistance, and dyslipidemia and these perturbations are linked to an increased risk of developing cardiometabolic disease. Pharmacological agonists of the glucagon-like peptide-1 (GLP1) receptor have been shown to offset weight-gain associated with chronic SGA administration and mitigate the acute metabolic side effects of SGAs.

CHOP is dispensable for exercise-induced increases in GDF15.

Growth differentiating factor-15 (GDF15) is expressed, and secreted, from a wide range of tissues and serves as a marker of cellular stress. A key transcriptional regulator of this hormone is the endoplasmic reticulum stress protein, CHOP (C/EBP homologous protein). Exercise increases GDF15 levels but the underlying mechanisms of this are not known.

AMPK mediates energetic stress-induced liver GDF15.

Growth differentiating factor-15 (GDF15) is an emerging target for the treatment of obesity and metabolic disease partly due to its ability to suppress food intake. GDF15 expression and secretion are thought to be regulated by a cellular integrated stress response, which involves endoplasmic reticulum (ER) stress. AMPK is another cellular stress sensor, but the relationship between AMPK, ER stress, and GDF15 has not been assessed in vivo.

Reactive oxygen species-dependent regulation of pyruvate dehydrogenase kinase-4 in white adipose tissue.

Reactive oxygen species (ROS) are important signaling molecules mediating the exercise-induced adaptations in skeletal muscle. Acute exercise also drives the expression of genes involved in reesterification and glyceroneogenesis in white adipose tissue (WAT), but whether ROS play any role in this effect has not been explored. We speculated that exercise-induced ROS would regulate acute exercise-induced responses in WAT.