“This discovery unveils a potential novel molecular target for therapeutic strategies against hepatic steatosis during the aging process […]”

BUFFALO, NY- March 20, 2024 – A new research paper was published in Aging (listed by MEDLINE/PubMed as “Aging (Albany NY)” and “Aging-US” by Web of Science) Volume 16, Issue 5, entitled, “FoxO6-mediated ApoC3 upregulation promotes hepatic steatosis and hyperlipidemia in aged rats fed a high-fat diet.”

FoxO6, an identified factor, induces hyperlipidemia and hepatic steatosis during aging by activating hepatic lipoprotein secretion and lipogenesis leading to increased ApoC3 concentrations in the bloodstream. However, the intricate mechanisms underlying hepatic steatosis induced by elevated FoxO6 under hyperglycemic conditions remain intricate and require further elucidation.

In this new study, researchers Dae Hyun Kim, Seulah Lee, Sang Gyun Noh, Jaewon Lee, and Hae Young Chung from Pusan National University aimed to delineate the regulatory pathway involving ApoC3 controlled by FoxO6 and its resultant functional impacts.

“[…] we employed a spectrum of models including liver cell cultures, aged rats subjected to HFD, transgenic mice overexpressing FoxO6 (FoxO6-Tg), and FoxO6 knockout mice (FoxO6-KO).”

Their findings indicate that FoxO6 triggered ApoC3-driven lipid accumulation in the livers of aged rats on an HFD and in FoxO6-Tg, consequently leading to hepatic steatosis and hyperglycemia. Conversely, the absence of FoxO6 attenuated the expression of genes involved in lipogenesis, resulting in diminished hepatic lipid accumulation and mitigated hyperlipidemia in murine models. Additionally, the upregulation of FoxO6 due to elevated glucose levels led to increased ApoC3 expression, consequently instigating cellular triglyceride mediated lipid accumulation. The transcriptional activation of FoxO6 induced by both the HFD and high glucose levels resulted in hepatic steatosis by upregulating ApoC3 and genes associated with gluconeogenesis in aged rats and liver cell cultures.

“Our conclusions indicate that the upregulation of ApoC3 by FoxO6 promotes the development of hyperlipidemia, hyperglycemia, and hepatic steatosis in vivo, and in vitro. Taken together, our findings underscore the significance of FoxO6 in driving hyperlipidemia and hepatic steatosis specifically under hyperglycemic states by enhancing the expression of ApoC3 in aged rats.”
 

Read the full paper: DOI: https://doi.org/10.18632/aging.205610 

Corresponding Author: Hae Young Chung

Corresponding Email: hyjung@pusan.ac.kr 

Keywords: HFD-feeding, aging, forkhead transcription factor O6, ApoC3, lipid accumulation, hepatic steatosis

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About Aging:

Aging publishes research papers in all fields of aging research including but not limited, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer’s diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases.

Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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The Advanced Research Projects Agency for Health (ARPA-H) has appointed Etta D. Pisano, MD, FACR, senior portfolio lead, to build the agency’s clinical trial portfolio and lead the ARPA-H Advancing Clinical Trials Readiness Initiative under ARPA-H Resilient Systems Mission Office Director Jennifer Roberts.

The first radiologist to be appointed to such a role, Dr. Pisano is an internationally recognized expert in women’s health, breast cancer research, and the use of artificial intelligence in medical imaging applications.

“I am honored to be working for ARPA-H to identify and promote research that can improve healthcare quality, efficacy and delivery, and to improve patient care and access to clinical trials for all Americans, including women, rural residents, and the underserved,” said Dr. Pisano.

Dr. Pisano will continue to serve as study chair of the large-scale Tomosynthesis Mammographic Imaging Screening Trial (TMIST) for the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN). TMIST is led by ECOG-ACRIN with funding from the National Cancer Institute, part of the National Institutes of Health. She will also continue to serve as the American College of Radiology® (ACR®) Chief Research Officer (CRO). Dr. Pisano previously served as the principal investigator of the landmark Digital Mammographic Imaging Screening Trial (DMIST).

The TMIST breast cancer screening study is among the fastest growing National Cancer Institute (NCI) trials of the COVID-19 era. Under Dr. Pisano’s leadership, TMIST is assembling one of the most diverse cancer screening trial populations ever. Approximately 21% of TMIST U.S. participants are Black—more than double the average rate for Black participation in NCI-funded clinical trials (9%).

With ARPA-H, Dr. Pisano will work to build underserved and minority participation in clinical trials—including identifying and onboarding rural facilities and those outside of large academic medical centers—such as emerging retail healthcare sites. 

These duties are also very consistent with the missions of ECOG-ACRIN and ACR, which include promoting the exploration and identification of next-generation technologies that can benefit patients and providers.

“This is a great opportunity for Etta, and I’m excited about the impact she will make on our approach to clinical trials,” said Mitchell D. Schnall, MD, PhD, group co-chair of ECOG-ACRIN.

About ECOG-ACRIN

The ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) is an expansive membership-based scientific organization that designs and conducts cancer research involving adults who have or are at risk of developing cancer. The Group comprises nearly 1400 member institutions and 21,000 research professionals in the United States and around the world. ECOG-ACRIN is known for advancing precision medicine and biomarker research through its leadership of major national clinical trials integrating cutting-edge genomic approaches. Member researchers and advocates collaborate across more than 40 scientific committees to design studies spanning the cancer care spectrum, from early detection to management of advanced disease. ECOG-ACRIN is funded primarily by the National Cancer Institute, part of the National Institutes of Health. Visit ecog-acrin.org, and follow us on X @eaonc, Facebook, LinkedIn, and Instagram.

Media Contact: Diane Dragaud, Director of Communications, communications@ecog-acrin.org.