Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes.

By M. Bordicchia, Dianxin Liu, E. Amri, G. Ailhaud, P. Dessì‐Fulgheri, Chaoying Zhang, N. Takahashi, R. Sarzani, S. Collins. Journal of Clinical Investigation, 2012

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The ability of mammals to resist body fat accumulation is linked to their ability to expand the number and activity of "brown adipocytes" within white fat depots. Activation of β-adrenergic receptors (β-ARs) can induce a functional "brown-like" adipocyte phenotype. As cardiac natriuretic peptides (NPs) and β-AR agonists are similarly potent at stimulating lipolysis in human adipocytes, we investigated whether NPs could induce human and mouse adipocytes to acquire brown adipocyte features, including a capacity for thermogenic energy expenditure mediated by uncoupling protein 1 (UCP1). In human adipocytes, atrial NP (ANP) and ventricular NP (BNP) activated PPARγ coactivator-1α (PGC-1α) and UCP1 expression, induced mitochondriogenesis, and increased uncoupled and total respiration. At low concentrations, ANP and β-AR agonists additively enhanced expression of brown fat and mitochondrial markers in a p38 MAPK-dependent manner. Mice exposed to cold temperatures had increased levels of circulating NPs as well as higher expression of NP signaling receptor and lower expression of the NP clearance receptor (Nprc) in brown adipose tissue (BAT) and white adipose tissue (WAT). NPR-C(-/-) mice had markedly smaller WAT and BAT depots but higher expression of thermogenic genes such as Ucp1. Infusion of BNP into mice robustly increased Ucp1 and Pgc-1α expression in WAT and BAT, with corresponding elevation of respiration and energy expenditure. These results suggest that NPs promote "browning" of white adipocytes to increase energy expenditure, defining the heart as a central regulator of adipose tissue biology.

Subfields: Cardiology and Cardiovascular Medicine, Epidemiology, Physiology

View Paper: https://www.semanticscholar.org/paper/3dd8decc509ce98e9da3246f326c6af34ee39a1e

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In Cardiology and Cardiovascular Medicine

1. B. Palmer
2. D. Clegg
3. B. Spiegelman

In Epidemiology

1. S. Kajimura
2. B. Spiegelman
3. P. Seale
4. H. Ohno
5. B. Palmer
6. D. Clegg
7. Jun Wu
8. Kosaku Shinoda

In Physiology

1. S. Kajimura
2. P. Seale
3. B. Spiegelman
4. Jun Wu
5. P. Cohen
6. H. Ohno
7. B. Palmer
8. D. Clegg

Citations in the corpus

• Irisin Stimulates Browning of White Adipocytes Through Mitogen-Activated Protein Kinase p38 MAP Kinase and ERK MAP Kinase Signaling (2014, background): “Taking into account the relationship between irisin and energy expenditure, irisin can now be regarded as another secreted protein stimulating brown adipocyte thermogenesis, besides liver fibroblast growth factor 21 (18) and cardiac natriuretic peptides (19).”
• Human BAT Possesses Molecular Signatures That Resemble Beige/Brite Cells (2012, background): “Alternatively, using endogenous hormones such as FGF21 [49], natriuretic peptides [50], prostaglandin [51,52], or Irisin [53] to promote browning of white fat would be a plausible approach.”
• Brown and beige fat: Physiological roles beyond heat-generation (2015, background): “, 2014), natriuretic peptides (Bordicchia et al., 2012), prostaglandins (Madsen et al.”
• The sexual dimorphism of obesity (2015, positive): “3), which have recently been demonstrated to facilitate browning of white adipose tissues by up regulation of UCP-1 and by activating mitochondrial biogenesis and uncoupling in white adipose tissues (Bordicchia et al., 2012; Collins, 2014).”
• Adaptive thermogenesis in adipocytes: is beige the new brown? (2013, background): “Moreover, BNP infusion in mice induces UCP1 expression in both BAT and inguinal subcutaneous WAT and increases system energy expenditure (Bordicchia et al. 2012).”
• Brown and beige fat in humans: thermogenic adipocytes that control energy and glucose homeostasis. (2015, neutral): “As listed in Figure 3, such factors include BMP4 (66), BMP7 (67, 68), BMP8b (69), FGF19 (70, 71), FGF21 (72, 73), growth differentiation factor-5 (GDF5) (74), natriuretic peptides (75), prostaglandins (76, 77), VEGF (78, 79), and β-aminoisobutyric acid (BAIBA) (80).”