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. 2013 Jun;62(6):1774-82.
doi: 10.2337/db12-1665.

Banting Lecture 2012: Regulation of adipogenesis: toward new therapeutics for metabolic disease

Bruce M Spiegelman  1
Affiliations

Banting Lecture 2012: Regulation of adipogenesis: toward new therapeutics for metabolic disease

Bruce M Spiegelman. Diabetes. 2013 Jun.

Abstract

The Banting Medal for Scientific Achievement Award is the American Diabetes Association's highest scientific award and honors an individual who has made significant, long-term contributions to the understanding of diabetes, its treatment, and/or prevention.The award is named after Nobel Prize winner Sir Frederick Banting, who codiscovered insulin treatment for diabetes. Bruce M. Spiegelman, PhD, of Harvard Medical School and the Dana-Farber Cancer Institute in Boston, received the American Diabetes Association's Banting Medal for Scientific Achievement at the Association's 72nd Scientific Sessions, 8-12 June 2012, Philadelphia, Pennsylvania. He presented the Banting Lecture, "Transcriptional Control of Adipogenesis-Toward a New Generation of Therapeutics for Metabolic Disease," on Sunday, 10 June 2012. In his lecture, Dr. Spiegelman described the discovery of several transcriptional components that control adipose cell development: PPAR-γ, PGC1-α, and PRDM16. He also described the cloning and characterization of beige fat cells, the thermogenic "brown-like" cells that can develop in white fat depots. Lastly, Dr. Spiegelman discussed irisin, a newly discovered regulatory hormone that converts white fat into the more thermogenic beige fat. Dr. Spiegelman's research has found that irisin, which is induced by exercise, appears to activate some of the same health benefits as exercise, including improvement of glycemic control. Understanding the regulation of adipose tissue, white, brown, and beige, can potentially lead to the development of a new generation of therapeutics for diabetes prevention and treatment.

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Figures

FIG. 1.
FIG. 1.
The general features of white and brown adipocytes. Key transcriptional regulators that are discussed in this article are shown in yellow.
FIG. 2.
FIG. 2.
PET images of an individual human at three different angles at ambient temperature and after brief cold exposure (6). CT, computed tomography; BAT, brown adipose tissue.
FIG. 3.
FIG. 3.
Suppression of PRDM16 expression with a specific shRNA causes a phenotypic switch to myotubes in brown fat cell cultures. For further details, see ref. . shSCR, scrambled shRNA.
FIG. 4.
FIG. 4.
Forced expression of PRDM16 causes brown adipogenesis in C2C12 myoblasts. For further details, see ref. . ctl, control.
FIG. 5.
FIG. 5.
Illustration of three distinct types of adipose cells (17).
FIG. 6.
FIG. 6.
Glucose tolerance test performed in high fat–fed control mice and mice with adipose-specific expression of PRDM16 (10).
FIG. 7.
FIG. 7.
Medium conditioned by cells expressing PGC1-α have a “browning effect” on primary inguinal adipose cells with the induction of UCP1. For further details, see ref. . *P < 0.05.
FIG. 8.
FIG. 8.
FNDC5 protein stimulates UCP1 expression in inguinal adipose cell cultures. BMP7 and FNDC5 were used at the doses shown for 4 days. For further details, see ref. . Sub-Q, subcutaneous.
FIG. 9.
FIG. 9.
A fragment of FNDC5 protein is secreted when the cDNA encoding FNDC5 is expressed in 293 cells. FNDC5-derived protein was detected by Western blotting. For further details, see ref. . H, hydrophobic domain. SP, signal peptide.
FIG. 10.
FIG. 10.
The amino acid sequence of FNDC5 and irisin (underlined), the secreted fragment of FNDC5. For further details, see ref. . C, C-terminal region. H, hydrophobic domain. SP, signal peptide.
FIG. 11.
FIG. 11.
Alignment of amino acid sequences for human and mouse irisin.
FIG. 12.
FIG. 12.
Effects of adenoviral expression of FNDC5 on the browning of inguinal adipose tissue in mice. For further details, see ref. . Ad, adenovirus expression vector. Adipo, AdipoQ. *P < 0.05.
FIG. 13.
FIG. 13.
Fasting insulin levels and glucose tolerance in mice receiving adenoviral vectors expressing FNDC5. For further details, see ref. . *P < 0.05.
FIG. 14.
FIG. 14.
Model of irisin secretion and actions.
FIG. 15.
FIG. 15.
Molecular characteristics of beige adipocytes. Note that these cells have very low basal UCP1 mRNA expression, but induce it robustly upon cAMP stimulation. For further details, see ref. . BAT, brown adipose tissue. N.S., not significant. ***P < 0.05.
FIG. 16.
FIG. 16.
Human adult “brown fat” has the molecular signature of beige adipose cells. Biopsies of human PET-positive brown fat and neighboring white fat depots were taken, and RNA was prepared. qPCR was performed for UCP1 and beige and brown selective mRNAs. For further details, see ref. . BAT, brown adipose tissue. WAT, white adipose tissue.
FIG. 17.
FIG. 17.
Alternative models for how irisin can bring about thermogenic actions on beige cells.
FIG. 18.
FIG. 18.
Irisin functions preferentially on beige cells and does not cause a change in cell fate. hFC, human FC fragment of IgG. *P < 0.05.
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References

    1. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 1993;259:87–91 - PubMed
    1. Tontonoz P, Hu E, Spiegelman BM. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell 1994;79:1147–1156 - PubMed
    1. Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 1998;92:829–839 - PubMed
    1. Seale P, Kajimura S, Yang W, et al. Transcriptional control of brown fat determination by PRDM16. Cell Metab 2007;6:38–54 - PMC - PubMed
    1. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, et al. Cold-activated brown adipose tissue in healthy men. N Engl J Med 2009;360:1500–1508 - PubMed

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