Identification of a Lipokine, a Lipid Hormone Linking Adipose Tissue to Systemic Metabolism

By Haiming Cao, K. Gerhold, J. Mayers, Michelle M. Wiest, Steven M. Watkins, G. Hotamışlıgil. Cell, 2008

1,125 citations recorded by the source corpus.

Dysregulation of lipid metabolism in individual tissues can lead to systemic disruption of insulin action and glucose metabolism. Utilizing a comprehensive lipidomic platform and mice deficient in adipose tissue lipid chaperones aP2 and mal1, we explored how metabolic alterations in adipose tissue are linked to whole-body metabolism through lipid signals. A robust increase in de novo lipogenesis rendered the adipose tissue of these mice resistant to the deleterious systemic effects of dietary lipid exposure. Systemic lipid profiling also led to identification of C16:1n7-palmitoleate as an adipose tissue-derived lipid hormone that strongly stimulates muscle insulin action and suppresses hepatosteatosis. Our data reveal a novel, lipid-mediated endocrine network and demonstrate that adipose tissue uses lipokines such as C16:1n7-palmitoleate to communicate with distant organs and regulate systemic metabolic homeostasis.

Subfields: Biochemistry, Epidemiology, Physiology

View Paper: https://www.semanticscholar.org/paper/2bfbf17fbc36c732f396c2f841bfbe06a4fb1da9

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Biochemistry

In Epidemiology

In Physiology

Citations in the corpus

INFLAMMATION AND LIPID SIGNALING IN THE ETIOLOGY OF INSULIN RESISTANCE (2012, positive): “Circulating C16:1N7 levels are directly correlated with insulin sensitivity in mice and that inhibition of C16:1N7 production can cause insulin resistance (Cao et al., 2008).”
Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects (2014, background): “However, certain fatty acids such as dietary omega-3 fatty acids (Oh et al., 2010; Virtanen et al., 2014) and the endogenously produced palmitoleate (Cao et al., 2008) have favorable metabolic effects.”
Palmitic Acid: Physiological Role, Metabolism and Nutritional Implications (2017, background): “Another confounding factor is the role of fatty acids binding proteins (FABP), indeed Cao et al. (2008), found that FABP greatly determined the impact of dietary fat on adipose lipid composition andmetabolism.”
Extracellular miRNAs: From Biomarkers to Mediators of Physiology and Disease (2019, background): “, 2016), signaling lipids (Cao et al., 2008; Lynes et al., 2017; Stanford et al., 2018; Yore et al., 2014), inflammatory mediators (Brestoff and Artis, 2015; Glass and Olefsky, 2012; Mathis, 2013), and miRNAcontaining EVs.”
The key roles of elongases and desaturases in mammalian fatty acid metabolism: Insights from transgenic mice. (2010, background): “contributes to the regulation of global lipid homeostasis [2] is of considerable importance.”
SIRT3 Deficiency and Mitochondrial Protein Hyperacetylation Accelerate the Development of the Metabolic Syndrome (2011, neutral): “The Scd1 promoter region (1–1500) was cloned in front of a luciferase gene and packaged into an adenoviral reporter (Cao et al., 2008).”
Adipocytokines in Obesity and Metabolic Disease (2014, positive): “But fatty acids in this setting have often been considered as a whole, and studies examining the distinct impact of individual lipid species have provided intriguing insights into the specificities of adipose-secreted lipids (Cao et al. 2008).”
Stearoyl CoA desaturase is required to produce active, lipid-modified Wnt proteins (2013, background): “Palmitoleic acid is a rare fatty acid and its distribution in cells is highly regulated (Cao et al., 2008).”
Endoplasmic Reticulum Stress and the Inflammatory Basis of Metabolic Disease (2010, positive): “Certain free fatty acids can induce JNK activation directly or indirectly resulting in insulin resistance in adipocytes, hepatocytes, and pancreatic islets, whereas others mediate beneficial hormonal and metabolic effects (Cao et al., 2008).”
Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human (2012, background): “…the reduced C16:1n7 palmitoleate may explain the systemic metabolic disorders observed in GPR120-deficient mice on HFD, as palmitoleate has been proposed as a bioactive lipid by which adipose tissue communicates with distant organs (such as liver) and regulates systemic metabolic homeostasis 4 .”
Biochemical and physiological function of stearoyl-CoA desaturase. (2009, background): “16:0) within various tissues, and this is of direct importance because recent investigations have established a role for adipose-derived palmitoleic acid (16:1n7) as a lipokine that regulates whole body lipid metabolism (9).”