PPAR agonists induce a white-to-brown fat conversion through stabilization of PRDM16 protein

By H. Ohno, Kosaku Shinoda, B. Spiegelman, S. Kajimura. Cell Metabolism, 2012

750 citations recorded by the source corpus.

Brown adipose tissue dissipates energy through heat and functions as a defense against cold and obesity. PPAR ligands have been shown to induce the browning of white adipocytes; however, the underlying mechanisms remain unclear. Here we show that PPAR ligands require full agonism to induce a brown fat gene program preferentially in subcutaneous white adipose. These effects require expression of PRDM16, a factor that controls the development of classical brown fat. Depletion of PRDM16 blunts the effects of the PPAR agonist rosiglitazone on the induced brown fat gene program. Conversely, PRDM16 and rosiglitazone synergistically activate the brown fat gene program in vivo. This synergy is tightly associated with an increased accumulation of PRDM16 protein, due in large measure to an increase in the half-life of the protein in agonist treated cells. Identifying compounds that stabilize PRDM16 protein may represent a plausible therapeutic pathway for the treatment of obesity and diabetes.

Subfields: Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/c068fe07a6bf8f7b461778e3c174109da65cebcc

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. B. Spiegelman
2. S. Kajimura
3. P. Seale
4. L. Sidossis
5. Jun Wu
6. D. Mathis
7. Gerald I. Shulman
8. David W. Piston

In Physiology

1. S. Kajimura
2. B. Spiegelman
3. L. Sidossis
4. P. Seale
5. Jun Wu
6. P. Cohen
7. Alexander Sakers
8. H. Ohno

Citations in the corpus

• Adaptive thermogenesis in adipocytes: is beige the new brown? (2013, background): “A depot-dependent discrepancy between PRDM16 mRNA and protein levels was noted, likely caused by differential stability of PRDM16 in subcutaneous and visceral white adipose (Ohno et al. 2012).”
• Brown and beige fat in humans: thermogenic adipocytes that control energy and glucose homeostasis. (2015, positive): “Importantly, cold- and PPARγ agonist–induced WAT browning is substantially impaired in the absence of PRDM16 or EHMT1, indicating that these regulators mediate environment-induced beige adipocyte development (88, 91, 92).”
• Human BAT Possesses Molecular Signatures That Resemble Beige/Brite Cells (2012, background): “Our recent study has also shown that PRDM16 is required for the development of beige cells (so called ‘‘browning’’ of white fat) in response to PPARc agonists in mice [28].”
• Ablation of PRDM16 and Beige Adipose Causes Metabolic Dysfunction and a Subcutaneous to Visceral Fat Switch (2014, background): “However, PRDM16 also appears to be involved in the development and function of beige cells (Ohno et al., 2012; Seale et al., 2011).”
• Adipose tissue plasticity in health and disease (2022, background): “Interestingly, sustained use of synthetic PPAR g agonists, like TDZs, can promote thermogenic gene expression in a PRDM16-dependent manner (Ohno et al., 2012).”
• Brown and beige fat: Physiological roles beyond heat-generation (2015, methodology): “previously shown that PRDM16 potently represses the muscleselective or WAT-selective gene programs in a EHMT1-dependent fashion (Harms et al., 2014; Ohno et al., 2013).”