# Regulation of hepatic lipid metabolism by novel protein BASIC

> **NIH NIH F30** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $39,236

## Abstract

PROJECT SUMMARY
Non-alcoholic fatty liver disease (NAFLD) affects 25% of the US adult population and is associated with
obesity, insulin resistance and cardiovascular disease. Furthermore, approximately 20% of NAFLD patients
(13-16 million people) develop liver fibrosis, which is associated with a higher risk of hepatocellular carcinoma,
cirrhosis and liver failure. Unfortunately, there are few effective treatments for NAFLD, aside from lifestyle
modification and liver transplant. Excess neutral lipids are stored in lipid droplets (LDs)–dynamic organelles
that quickly expand and shrink depending on the metabolic needs of the cell. Importantly, LD morphology and
abundance are determined by the fusion or lipolysis of existing LDs. Recent studies have led to the discovery
of a novel protein named BASIC, an endoplasmic reticulum-lipid droplet protein that promotes a multilocular
phenotype and increases lipid utilization in brown adipocytes. BASIC is expressed in white and brown adipose
tissue, and liver. In adipocytes, BASIC inhibits LD fusion proteins CIDEA and CIDEC, preventing expansion of
LD size. CIDEB, the primary CIDE protein expressed in liver, has been shown to promote VLDL secretion,
decrease triglyceride and cholesterol synthesis, and inhibit b-oxidation in hepatocytes. However, the
physiologic or pathologic contexts in which the liver requires small, BASIC+ LDs for optimal function remain to
be determined. Interestingly, global, but not adipose-specific deletion of BASIC decreases fat mass in chow-
fed mice, pointing to adipose-independent effects on systemic energy balance. Preliminary data indicate that
BASIC is a PPARa target gene whose expression is highly induced by both fasting and western diet feeding.
Acute overexpression of BASIC decreases plasma lipids, suggesting this protein regulates hepatic lipid
metabolism. The proposed research plan will elucidate the hepatic mechanism of action by characterizing how
BASIC regulates LD biology and define molecular interaction partners in vitro (Aim 1a). Furthermore, the
pathway(s) affected by hepatic BASIC expression (beta-oxidation, lipogenesis, lipoprotein secretion) will be
determined (Aim 1b). In vivo studies using gain- and loss-of-function approaches in mice will characterize the
role of BASIC in fasting and in response to high-fat diet feeding (Aim 2). Completion of the proposed aims will
provide insight for the function of a novel PPARa target gene, which will contribute to the growing
understanding of hepatic lipid droplet biology and may reveal novel opportunities for therapeutics in
dyslipidemia and hepatic steatosis.

## Key facts

- **NIH application ID:** 10645095
- **Project number:** 5F30DK134050-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Lauren F Uchiyama
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $39,236
- **Award type:** 5
- **Project period:** 2022-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10645095

## Citation

> US National Institutes of Health, RePORTER application 10645095, Regulation of hepatic lipid metabolism by novel protein BASIC (5F30DK134050-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10645095. Licensed CC0.

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