Elevated adipose inflammation, but reduced hepatic triacylglycerol storage in diet-induced obese Plin4^-/- mice

Plin4 is transcriptionally regulated by peroxisome proliferator-activated receptor gamma and is primarily expressed in white adipose tissue (WAT). We found that expression of Plin4 is elevated in the liver upon prolonged feeding with an obesogenic diet containing saturated fat, fructose, and cholesterol (Western diet). To investigate the functional role of Plin4 in energy metabolism, we generated Plin4^-/- mice and assessed effects upon Plin4 removal in the liver, WAT, and skeletal muscle. Lean Plin4^-/- mice fed a chow diet had no clear phenotype, except for slightly altered expression of Plin5 in the heart, liver, and WAT. Obese female Plin4^-/- mice fed a Western diet had normal metabolic rate, but elevated insulin levels and faster glucose clearance compared to Plin4^+/+ mice. The livers of Plin4^-/- mice fed a Western diet had normal cholesteryl ester levels, reduced triacylglyceride levels, and reduced expression of endoplasmic reticulum stress markers downstream of PERK. Ovarian WAT of Plin4^-/- mice fed a Western diet had elevated expression of macrophage markers, higher presence of crown-like structures, but normal adipocyte cell size. In summary, Plin4 deficiency results in subtle systemic effects in diet-obese mice, affecting hepatic lipid storage and adipose inflammation.