Pengpeng Bi

University of Georgia | UGA · Center for Molecular Medicine & Department of Genetics

Obesity and metabolic disorders caused by energy surplus pose an increasing concern within the global population. Brown adipose tissue (BAT) dissipates energy through mitochondrial non‐shivering thermogenesis, thus representing a powerful agent against obesity. Here we explore the novel role of a mitochondrial outer membrane protein, LETM1‐domain c...

Muscle precursor cells known as myoblasts are essential for muscle development and regeneration. Notch signaling is an ancient intercellular communication mechanism that plays prominent roles in controlling the myogenic program of myoblasts. Currently whether and how the myogenic cues feedback to refine Notch activities in these cells are largely u...

The size of an animal is determined by the size of its musculoskeletal system. Myoblast fusion is an innovative mechanism that allows for multinucleated muscle fibers to compound the size and strength of individual mononucleated cells. However, the evolutionary history of the control mechanism underlying this important process is currently unknown....

The size of an animal is determined by the size of its musculoskeletal system. Myoblast fusion is an innovative mechanism that allows for multinucleated muscle fibers to compound the size and strength of individual mononucleated cells. However, the evolutionary history of the control mechanism underlying this important process is currently unknown....

The Cre/loxP system is a powerful tool for gene function study in vivo. Regulated expression of Cre recombinase mediates precise deletion of genetic elements in a spatially- and temporally-controlled manner. Despite the robustness of this system, it requires a great amount of effort to create a conditional knockout model for each individual gene of...

Myoblast fusion is essential for formations of myofibers, the basic cellular and functional units of skeletal muscles. Recent genetic studies in mice identified two long-sought membrane proteins, Myomaker and Myomixer, which cooperatively drive myoblast fusion. It is unknown whether and how human muscles, with myofibers of tremendously larger size,...

Significance Skeletal muscle damaged by injury or disease can regenerate new muscle fibers. The regenerative properties of skeletal muscle involve fusion of activated muscle stem cells (satellite cells). We recently discovered Myomixer, a conserved micropeptide that is specifically expressed during muscle formation. Myomixer, together with its part...

Significance The formation of skeletal muscle fibers during embryogenesis and adult injury-induced muscle repair occurs through the fusion of myoblasts. We recently discovered myomixer, a muscle-specific micropeptide required for myoblast fusion in mice. Myomixer and myomaker, another muscle-specific membrane protein, are sufficient to induce fusio...

Micromanaging muscle cell fusion Adult skeletal muscles are characterized by long, multinucleated cells called myofibers. Myofibers form when muscle precursor cells, or myoblasts, differentiate and fuse together during embryogenesis. The fusion process is not fully understood. Studying cell culture and mouse models, Bi et al. identified an 84–amino...

Satellite cells (SCs) are myogenic stem cells required for regeneration of adult skeletal muscles. A proper balance among quiescence, activation and differentiation is essential for long-term maintenance of SCs and their regenerative function. Here we show a function of Pten (phosphatase and tensin homologue) in quiescent SCs. Deletion of Pten in q...

Supplementary Figures and Supplementary Tables

Skeletal muscle stem cells (satellite cells [SCs]) are normally maintained in a quiescent (G0) state. Muscle injury not only activates SCs locally, but also alerts SCs in distant uninjured muscles via circulating factors. The resulting GAlert SCs are adapted to regenerative cues and regenerate injured muscles more efficiently, but whether they prov...

Agilent microarray results showing genes up-regulated and down-regulated in N1ICD-mdx versus mdx muscles.DOI: http://dx.doi.org/10.7554/eLife.17355.013

ELife digest Muscles do much more than enable the body to move; they are also important organs involved in the metabolism. Conditions ranging from muscular dystrophy to insulin resistance result from problems that affect muscle tissue. Hence, understanding the signaling mechanisms that regulate how muscles develop and work will be critical to impro...

Liposarcomas (LPSs) are the most common soft-tissue cancer. Because of the lack of animal models, the cellular origin and molecular regulation of LPS remain unclear. Here, we report that mice with adipocyte-specific activation of Notch signaling (Ad/N1ICD) develop LPS with complete penetrance. Lineage tracing confirms the adipocyte origin of Ad/N1I...

Brown adipose tissue (BAT) dissipates energy through Ucp1-mediated uncoupled respiration and its activation may represent a therapeutic strategy to combat obesity. Here we show that Lkb1 controls BAT expansion and UCP1 expression in mice. We generate adipocyte-specific Lkb1 knockout mice and show that, compared with wild-type littermates, these mic...

Supplementary Figure 1-17 and Supplementary Table 1

Movement of WT (left) and Adipoq-Lkb1 (right) mice in the new cages.

Evolutionarily unprepared for modern high-calorie diets and sedentary lifestyles, humans are now unprecedentedly susceptible to metabolic disorders such as obesity, type 2 diabetes (T2D), nonalcoholic fatty liver, and cardiovascular disease. These metabolic conditions are intertwined, together known as metabolic syndrome, and compromise human life...

Stk11, commonly known as Lkb1, is a tumor suppressor that regulates cellular energy metabolism and stem cell function. Satellite cells are skeletal muscle resident stem cells that maintain postnatal muscle growth and repair. Here, we used MyoDCre/Lkb1flox/flox mice (called MyoD-Lkb1) to delete Lkb1 in embryonic myogenic progenitors and their descen...

The prevalence of obesity has risen to an unprecedented level. According to World Health Organization, over 500 million adults, equivalent to 10%–14% of the world population, were obese with a body mass index (BMI) of 30 kg/m2 or greater in 2008.11. Malik VS, Willett WC, Hu FB. Global obesity: trends, risk factors and policy implications. Nat Rev E...

Excessive intramyocellular triglycerides (muscle lipids) are associated with reduced contractile function, insulin resistance and Type 2 diabetes, but what governs lipid accumulation in muscle is unclear. Here we report a role of Lkb1 in regulating lipid metabolism in muscle stem cells and their descendent mature muscles. We used MyodCre and Lkb1fl...

One outcome of activation of the phosphatidylinositol 3-kinase (PI3K) pathway is increased aerobic glycolysis, but the upstream signaling events that regulate the PI3K pathway, and thus the Warburg effect, are elusive. Increasing evidence suggests that Plk1, a cell cycle regulator, is also involved in cellular events in addition to mitosis. To test...

Beige adipocytes in white adipose tissue (WAT) are similar to classical brown adipocytes in that they can burn lipids to produce heat. Thus, an increase in beige adipocyte content in WAT browning would raise energy expenditure and reduce adiposity. Here we report that adipose-specific inactivation of Notch1 or its signaling mediator Rbpj in mice re...

Relative expression of miroRNAs in various subcutaneous WAT depots. asWAT, anterior subcutaneous WAT; bsWAT, back subcutaneous WAT; ingWAT, inguinal WAT. The expression of bsWAT is normalized to 1. N = 3. *P<0.05, **P<0.01. (TIF)

Knockdown of miR-133a upregulates UCP1 expression. Depots of asWAT and ingWAT were harvested from widltype (WT) and miR-133a knockdown (KO; miR-133a1−/−a2+/−) mice that were housed at room temperature or at 4°C for 5 days. Pictured are representative Western Blot images showing the relative expression levels of UCP1. Beta-Actin is used as internal...

miR-133a inhibits adipocyte browning in SAT. SAT SVFs were transfected with synthetic miRNA133a by electroporation and cultured to confluence, followed by adipogenic induction and differentiation for 4 days each. (A–C) qPCR analysis of miR-133a and the brown markers after cells were differentiated. N = 3, *P<0.05, **P<0.01. (TIF)

Author Summary Global obesity and associated health issues have raised the significance of adipocyte biology. Adipose tissues are classified as brown and white adipose. White adipose tissues store lipids, leading to overweight, obesity, insulin resistance and Type2 diabetes. In contrast, brown adipose tissues use lipid storage to generate heat, inc...

Brown adipose tissues (BAT) are derived from a Myf5-expressing cell lineage and white adipose tissues (WAT) predominantly arise from non-Myf5 lineages, though a subpopulation of adipocytes in some WAT depots can be derived from the Myf5-lineage. However, the functional implication of the Myf5 and non-Myf5 lineage cells in WAT is unclear. We found t...

Myostatin (Mstn) is predominantly expressed in skeletal muscles and plays important roles in regulating muscle growth and development, as well as fat deposition. Mstn-knockout (Mstn(-/-)) mice exhibit increased muscle mass due to both hypertrophy and hyperplasia, and leaner body composition due to reduced fat mass. Here, we show that white adipose...

Microenvironmental oxygen (O(2)) regulates stem cell activity, and a hypoxic niche with low oxygen levels has been reported in multiple stem cell types. Satellite cells are muscle-resident stem cells that maintain the homeostasis and mediate the regeneration of skeletal muscles. We demonstrate here that hypoxic culture conditions favor the quiescen...

Notch signaling is a conserved cell fate regulator during development and postnatal tissue regeneration. Using skeletal muscle satellite cells as a model and through myogenic cell lineage-specific NICDOE (overexpression of constitutively activated Notch 1 intracellular domain), here we investigate how Notch signaling regulates the cell fate choice...

Stem cell niche plays a critical role in regulating the behavior and function of adult stem cells that underlie tissue growth, maintenance, and regeneration. In the skeletal muscle, stem cells, called satellite cells, contribute to postnatal muscle growth and hypertrophy, and thus, meat production in agricultural animals. Satellite cells are locate...