Neuregulin 4: A “Hotline” Between Brown Fat and Liver

Published on Oct 1, 2019in Obesity3.969
· DOI :10.1002/oby.22595
Matthias Blüher79
Estimated H-index: 79
(Leipzig University)
The discovery that functional brown adipose tissue (BAT) in adult humans is inversely related to body fat mass and may reflect metabolic health has stimulated adipose tissue research to explore activation of BAT as a potential target for antiobesity treatments. In addition to the capacity of BAT to increase energy expenditure and glucose and lipid uptake, BAT secretes factors that may contribute to the regulation of whole‐body metabolism. Among signals released from BAT, neuregulin 4 (NRG4) has been recently identified as an endocrine factor that may link the activation of BAT to protection against diet‐induced obesity, insulin resistance, and hepatic steatosis. NRG4 was shown to directly reduce lipogenesis in hepatocytes, and it could indirectly activate BAT via sympathetic neurons or via inducing brown adipocyte–like signatures in white adipocytes in a paracrine manner. However, the potential relevance of NRG4 as a diagnostic tool or target for the treatment of obesity‐related diseases remains to be explored.
  • References (12)
  • Citations (1)
📖 Papers frequently viewed together
7 Citations
3 Citations
21 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1Joan Villarroya (University of Barcelona)H-Index: 17
#2Rubén Cereijo (University of Barcelona)H-Index: 11
Last. Francesc Villarroya (University of Barcelona)H-Index: 40
view all 4 authors...
Background. The secretory properties of brown adipose tissue are thought to contribute to the association between active brown fat and a healthy metabolic status. Although a few brown adipokines have been identified, a comprehensive knowledge of the brown adipose tissue secretome is lacking. Methods. Here, to examine the effects of thermogenic activation of brown adipocytes on protein secretion, we used isobaric tags for relative and absolute quantification (iTRAQ) analysis to determine how the ...
1 CitationsSource
#1Vanessa Pellegrinelli (University of Cambridge)H-Index: 7
#2Vivian Peirce (University of Cambridge)H-Index: 5
Last. Antonio Vidal-Puig (University of Cambridge)H-Index: 78
view all 17 authors...
Activation of brown adipose tissue-mediated thermogenesis is a strategy for tackling obesity and promoting metabolic health. BMP8b is secreted by brown/beige adipocytes and enhances energy dissipation. Here we show that adipocyte-secreted BMP8b contributes to adrenergic-induced remodeling of the neuro-vascular network in adipose tissue (AT). Overexpression of bmp8b in AT enhances browning of the subcutaneous depot and maximal thermogenic capacity. Moreover, BMP8b-induced browning, increased symp...
11 CitationsSource
#1Kara L. Marlatt (Pennington Biomedical Research Center)H-Index: 9
#2Kong Y. Chen (NIH: National Institutes of Health)H-Index: 43
Last. Eric Ravussin (Pennington Biomedical Research Center)H-Index: 101
view all 3 authors...
To date, human studies show that brown adipose tissue (BAT) contributes a small yet highly variable amount to overall energy expenditure. No studies have shown a decrease in body weight with cold-i...
8 CitationsSource
#1Liang Guo (Fudan University)H-Index: 5
#2Peng Zhang (UM: University of Michigan)H-Index: 6
Last. Jiandie D. Lin (Life Sciences Institute)H-Index: 38
view all 9 authors...
23 CitationsSource
#1Yao Liu (Soochow University (Suzhou))H-Index: 4
#2Liming Song (Southern Medical University)H-Index: 2
Last. Jian-Ming Li (Soochow University (Suzhou))H-Index: 7
view all 11 authors...
9 CitationsSource
#1Francesc VillarroyaH-Index: 40
#2Rubén CereijoH-Index: 11
Last. Marta GiraltH-Index: 43
view all 4 authors...
In addition to undergoing adaptive thermogenesis, brown adipose tissue secretes a number of adipokines that can influence systemic metabolism. In this Review, Villarroya and colleagues discuss the current evidence for these so-called 'batokines' and how they might influence whole-body metabolic health.
135 CitationsSource
#1Alexander Pfeifer (University of Bonn)H-Index: 53
Brown adipose tissue (BAT) directly regulates energy homeostasis via uncoupling of mitochondrial ATP production and thermogenesis. Wang et al. (2014) now report that BAT controls liver lipogenesis via secretion of the growth factor NRG4.
16 CitationsSource
#1Guo Xiao Wang (UM: University of Michigan)H-Index: 8
#2Xu Yun Zhao (Life Sciences Institute)H-Index: 1
Last. Jiandie D. Lin (Life Sciences Institute)H-Index: 38
view all 13 authors...
The brown fat-derived neuregulin 4 regulates hepatic lipid homeostasis and whole-body insulin sensitivity
132 CitationsSource
#1Maria Chondronikola (HUA: Harokopio University)H-Index: 13
#2Elena VolpiH-Index: 54
Last. Lambros SidossisH-Index: 43
view all 16 authors...
Brown adipose tissue (BAT) has attracted scientific interest as an antidiabetic tissue owing to its ability to dissipate energy as heat. Despite a plethora of data concerning the role of BAT in glucose metabolism in rodents, the role of BAT (if any) in glucose metabolism in humans remains unclear. To investigate whether BAT activation alters whole-body glucose homeostasis and insulin sensitivity in humans, we studied seven BAT-positive (BAT+) men and five BAT-negative (BAT−) men under thermoneut...
309 CitationsSource
#1Meritxell Rosell (Imperial College London)H-Index: 4
#2Myrsini Kaforou (Imperial College London)H-Index: 9
Last. Mark Christian (Warw.: University of Warwick)H-Index: 31
view all 17 authors...
Brown adipocytes dissipate energy, whereas white adipocytes are an energy storage site. We explored the plasticity of different white adipose tissue depots in acquiring a brown phenotype by cold exposure. By comparing cold-induced genes in white fat to those enriched in brown compared with white fat, at thermoneutrality we defined a “brite” transcription signature. We identified the genes, pathways, and promoter regulatory motifs associated with “browning,” as these represent novel targets for u...
154 CitationsSource
Cited By1
#1Felipe Henriques (UMMS: University of Massachusetts Medical School)H-Index: 7
#2Alex H. Bedard (UMMS: University of Massachusetts Medical School)
Last. Batuhan Yenilmez (UMMS: University of Massachusetts Medical School)H-Index: 2
view all 12 authors...
The browning of inguinal white adipose tissue (iWAT) through increased abundance of thermogenic beige/brite adipocytes is induced by cold exposure and many other perturbations in association with beneficial systemic metabolic effects. Adipose browning is reported to require activation of sympathetic nerve fibers (SNF), aided by alternately activated macrophages within iWAT. Here we demonstrate the first example of a non-cell autonomous pathway for iWAT browning that is fully independent of SNF a...
#1Michael P. Czech (UMMS: University of Massachusetts Medical School)H-Index: 91
Abstract Background The diminished glucose lowering effect of insulin in obesity, denoted “insulin resistance”, is associated with glucose intolerance, type 2 diabetes and other serious maladies. Many thousands of publications on the topic have suggested dozens of hypotheses on the molecular and cellular disruptions that contribute to the syndrome. Yet there is still deep uncertainty on the mechanisms of its initiation and long term maintenance. Scope of review To simplify analysis of insulin re...
4 CitationsSource
#1Vian Azzu (Wellcome Trust)H-Index: 8
#1Vian Azzu (University of Cambridge)H-Index: 4
Last. Antonio Vidal-Puig (Wellcome Trust)H-Index: 78
view all 5 authors...
Abstract Adipose tissue and the liver play a significant role in the regulation of whole body energy homeostasis, but they have not evolved to cope with the continuous, chronic, nutrient surplus seen in obesity. In this review, we detail how prolonged metabolic stress leads to adipose tissue dysfunction, inflammation and adipokine release that results in increased lipid flux to the liver. Overall, the upshot of hepatic fat accumulation alongside an insulin resistant state, is that hepatic lipid ...
4 CitationsSource