on april 12, 2022, professor zhenji gan’s group at the model animal research center of nanjing university published a research paper titled “fnip1 regulates white adipose tissue browning and systemic glucose homeostasis by shaping intracellular calcium dynamics” in the journal of experimental medicine. this paper revealed a novel mechanism by which the fnip1 protein regulates thermogenic remodeling of white adipose tissue through the endoplasmic reticulum serca ca2 pump. the co-first authors of this paper are yujing yin, a doctoral student at nanjing university, dengqiu xu, a postdoctoral fellow, and yan mao, a doctoral student, while professor zhenji gan is the corresponding author. this work was highlighted by prof. lawrence kaza.
the benefits of beige adipocytes on metabolic health make it desirable therapeutic strategies to promote beige adipocytes thermogenic remodeling to treat obesity and metabolic diseases. the folliculin interacting protein 1 (fnip1) is implicated in the control of cellular metabolism via metabolic master regulators ampk and mtorc1. loss-of-function mutations of fnip1 have been reported in patients with altered cell metabolism. however, whether and how fnip1 controls the browning of white adipose tissue (wat) is unknown.
in this paper, the researchers discovered a crucial function of fnip1 in controlling wat browning that governs systemic glucose homeostasis (figure 1). using adipocyte-specific knockout mice and primary adipocytes in culture, we provided strong data that demonstrate fnip1 as a negative regulator of beige adipocyte thermogenesis. we also uncovered a novel molecular mechanism whereby fnip1 directly binds to and promotes the activity of serca, the main ca2 pump responsible for cytosolic ca2 removal, thereby dampening the ca2 -dependent thermogenic program. furthermore, the paper showed that the fnip1 pathway exerts profound effects on systemic glucose homeostasis and hepatic steatosis. thus, we discovered a novel fnip1-serca-intracellular ca2 pathway that regulates wat browning.
this work was supported by the national natural science foundation of china, the ministry of science and technology, the ministry of education, the jiangsu provincial department of science and technology, and the fundamental research funds for the central universities.
figure 1: model of fnip1 in the control of intracellular ca2 homeostasis and wat browning.
link to the paper:
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