Person:
Jang, Cholsoon

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Jang

First Name

Cholsoon

Name

Jang, Cholsoon
Author's Publications: search.filters.isAuthorOfPublication.5f361ed9-9529-4c85-936c-e9024ae8a64c

Search Results

Now showing 1 - 2 of 2
  • No Thumbnail Available
    Publication
    A metabolite of branched chain amino acids drives vascular fatty acid transport and causes glucose intolerance
    (2016-01-05) Jang, Cholsoon; D’Amore, Patricia A.; Loscalzo, Joseph; Cohen, David; Vander Heiden, Matthew
    Epidemiological and experimental data implicate branched chain amino acids (BCAAs) in the development of insulin resistance, but the mechanisms underlying this link remain unclear. Insulin resistance in skeletal muscle stems from excess accumulation of lipid species, a process that requires blood-borne lipids to first traverse the blood vessel wall. Little is known, however, of how this trans-endothelial transport occurs or is regulated. Here, we identify 3-hydroxy-isobutyrate (3-HIB), a catabolic intermediate of the BCAA valine, as a novel paracrine regulator of trans-endothelial transport of fatty acids. PGC-1α, a transcriptional co-activator that regulates broad programs of fatty acid consumption, induces the secretion from muscle of 3-HIB, which then triggers fatty acid uptake and transport in endothelial cells. Conversely, inhibiting the synthesis of 3-HIB in muscle cells blocks the promotion of endothelial fatty acid uptake. Providing animals with 3-HIB in drinking water, or inducing 3-HIB levels in skeletal muscle by over-expressing PGC-1α, stimulates muscle to take up fatty acids in vivo, leading to muscle lipid accumulation, and systemic glucose intolerance. 3-HIB levels are elevated in muscle from patients with diabetes. These data thus unveil a novel mechanism that regulates trans-endothelial flux of fatty acids, revealing 3-HIB as a new bioactive signaling metabolite that links the regulation of fatty acid flux to BCAA catabolism and provides a mechanistic explanation for how increased BCAA catabolic flux can cause diabetes.
  • Thumbnail Image
    Publication
    Cardiac Angiogenic Imbalance Leads to Peripartum Cardiomyopathy
    (Nature Publishing Group, 2012) Patten, Ian S.; Farrell, Caitlin; Tudorache, Igor; Bauersachs, Johann; Hilfiker-Kleiner, Denise; Rana, Sarosh; Shahul, Sajid; Rowe, Glenn C; Jang, Cholsoon; Liu, Laura; Hacker, Michele; Rhee, Julie S.; Mitchell, John; Mahmood, Feroze-Ud-Den; Hess, Philip; Koulisis, Nicole; Khankin, Eliyahu; Burke, Suzanne; Del Monte, Federica; Karumanchi, Subbian; Arany, Zoltan Pierre
    Peripartum cardiomyopathy (PPCM) is an often fatal disease that affects pregnant women who are near delivery, and it occurs more frequently in women with pre-eclampsia and/or multiple gestation. The aetiology of PPCM, and why it is associated with pre-eclampsia, remain unknown. Here we show that PPCM is associated with a systemic angiogenic imbalance, accentuated by pre-eclampsia. Mice that lack cardiac PGC-\(1\alpha\), a powerful regulator of angiogenesis, develop profound PPCM. Importantly, the PPCM is entirely rescued by pro-angiogenic therapies. In humans, the placenta in late gestation secretes VEGF inhibitors like soluble FLT1 (sFLT1), and this is accentuated by multiple gestation and pre-eclampsia. This anti-angiogenic environment is accompanied by subclinical cardiac dysfunction, the extent of which correlates with circulating levels of sFLT1. Exogenous sFLT1 alone caused diastolic dysfunction in wild-type mice, and profound systolic dysfunction in mice lacking cardiac PGC-\(1\alpha\). Finally, plasma samples from women with PPCM contained abnormally high levels of sFLT1. These data indicate that PPCM is mainly a vascular disease, caused by excess anti-angiogenic signalling in the peripartum period. The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM.