# MICT1 function in thermogenesis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $498,574

## Abstract

Obesity has become a global epidemic and is associated with type 2 diabetes and other chronic diseases.
While white adipose tissue is the primary energy storage organ, brown adipose tissue (BAT) dissipates energy
through non-shivering thermogenesis. Discovery of the presence of BAT/BAT-like tissues in human adults has
generated a considerable interest in BAT biology to design strategies against obesity and insulin resistance.
Recently, we have identified a new microprotein of 76 aa in length, highly expressed in BAT compared to other
tissues, and is induced upon cold exposure. Microproteins in general function by affecting protein-protein
interaction between signaling molecules. Our microprotein contains consensus docking motifs for Protein
Phosphatase 2B. Our preliminary studies showed that overexpression of this microprotein in differentiated BAT
cells increased oxygen consumption rate (OCR), while knockdown decreased OCR in basal and forskolin
stimulated conditions. Moreover, we detected higher PKA activity without changes in cAMP levels upon
overexpression of this microprotein in BAT cells. To document its physiological function, we have generated
conditional knockout mice and transgenic mice overexpressing the microprotein in UCP1+ cells and in
adipocytes. We propose that, our microprotein interacts with PP2B to regulate classic b-adrenergic
downstream signaling and potentiates PKA activity for promotion of thermogenesis. Aim 1 is to study its effect
on thermogenesis in differentiated brown adipocytes in culture. Aim 2 is to dissect the biochemical basis of its
function in promoting thermogenesis. Finally, Aim 3 is to evaluate its in vivo function in thermogenesis by loss-
and gain-of function studies in mice. This research may allow us to devise small molecule therapeutics to
increase thermogenesis for preventing obesity and improving insulin sensitivity in the future.

## Key facts

- **NIH application ID:** 10830337
- **Project number:** 5R01DK134757-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Hei Sook Sul
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $498,574
- **Award type:** 5
- **Project period:** 2023-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10830337

## Citation

> US National Institutes of Health, RePORTER application 10830337, MICT1 function in thermogenesis (5R01DK134757-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10830337. Licensed CC0.

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