# Age-related neuronal regulation of thermogenesis and lipid metabolism > **NIH NIH R15** · OHIO UNIVERSITY ATHENS · 2022 · $435,290 ## Abstract Project Summary Aging is associated with obesity, cardiovascular disease, and type 2 diabetes mellitus. Activating brown adipose tissue (BAT) thermogenesis in humans results in elevation of triglyceride clearance and insulin action, and has great potential to combat obesity, cardiovascular disease, and type 2 diabetes mellitus. We have reported in young adult mice that ACUTE injection of apolipoprotein A-IV(ApoA-IV): 1) elevates thermogenesis and uptake of fatty acid (FA) in BAT and 2) stimulates sympathetic neural activity (SNA) in BAT but reduces SNA in liver of chow-fed mice. However, its effect on lipid metabolism in adipose tissue and liver through alteration of SNA in old mice remains unknown. Chronic consumption of high-fat diet (HFD) suppresses ApoA-IV production normally induced by acute consumption of dietary lipids and attenuates SNA of BAT and thermogenesis. In this regard, we have preliminary evidence in young, HFD-fed mice that CHRONIC infusion of ApoA-IV: 1) elevates thermogenesis in BAT and beige adipose tissue (BeAT) and overall energy expenditure; 2) increases hepatic expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), implying restriction of hepatic lipogenesis; and 3) reduces hepatic and plasma lipid content, fat mass, and body weight gain. These findings suggest that chronic infusion of ApoA-IV alters lipid metabolism in BAT, BeAT and liver through neural or CEACAM1-mediated pathways. Because elderly humans and older rodents have a large decline in BAT activity, we theorize that the lower thermogenesis results in impaired lipid oxidation for energy combustion in BAT/BeAT, insufficient FA uptake into these adipose tissues, and elevated lipogenesis and lipid accumulation in the liver. Thus, we propose the innovative hypothesis that increased levels of ApoA-IV will act through sympathetic innervation to elevate lipid oxidation and uptake in BAT/BeAT and through CEACAM1-mediated reduction of lipogenesis in liver, subsequently reducing hepatic and plasma triglyceride (TG) in old, obese animals. This hypothesis will be tested using comprehensive, innovative, well-designed approaches. Aim 1 will investigate ApoA-IV’s role in sympathetic activation of BAT/BeAT to reverse age-attenuated thermogenesis. Aim 2 will investigate ApoA-IV’s effects on BAT/BeAT and hepatic lipid metabolism through neural or CEACAM1- mediated pathways to lower hepatic and plasma triglycerides. A major strength of this proposal is the interdisciplinary collaboration between Drs. Chunmin Lo (lipid metabolism & neurophysiology) and Haifei Shi (neuroendocrine & adipose biology) with support from Drs. Sonia Najjar (aging & CEACAM1-meidated insulin action), Darlene Berryman (aging & hormones) and Karen Coschigano (molecular biology & signaling pathways). As demonstrated by the strong preliminary data, these investigators have productively collaborated and will delineate the novel mechanism of ApoA-IV in downregulation of age-related ob... ## Key facts - **NIH application ID:** 10513891 - **Project number:** 1R15AG078768-01 - **Recipient organization:** OHIO UNIVERSITY ATHENS - **Principal Investigator:** Chunmin C. Lo - **Activity code:** R15 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2022 - **Award amount:** $435,290 - **Award type:** 1 - **Project period:** 2022-08-15 → 2024-12-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10513891 ## Citation > US National Institutes of Health, RePORTER application 10513891, Age-related neuronal regulation of thermogenesis and lipid metabolism (1R15AG078768-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10513891. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*