Comics take on: Leptin

Leptin is an important hormone that regulates satiety. Here we look at the associations that we find in The Molecular Human.

Click here to access the network on comics

The associations with the multiomics traits reflect known leptin biology

Most of the associations with leptin appear biologically plausible and are supported by the scientific literature, such as:

Body temperature: This Google Search brings up multiple research papers that support/investigate the role of leptin in body temperature regulation.
Insulin: The link between insulin and leptin should be evident – here a well-cited paper on the role of leptin in the control of insulin-glucose axis.
BMI: Mice that lack leptin become obese – see the Wikipedia page on the ob/ob mouse.
SEX: The association of leptin with sex (independent of BMI) has been established, and confirmed in GWAS with proteomics (see supplement of Sun et al., Nature, 2018).
CXCL5 expression: This paper reports high levels of expression and secretion of the chemokine CXCL5 in the macrophage fraction of white adipose tissue (WAT). Moreover, the authors found that CXCL5 is dramatically increased in serum of human obese compared to lean subjects.
6-Sialyl-N-acetyllactosamine in urine: According to HMDB this metabolite (HMDB0006584) is an oligosaccharide widely distributed among tissues and is involved in biological processes such as the regulation of the immune response and the progression of colon cancer. Its association with leptin is not immediately clear.
Sphingolipids and phospolipds: These related lipid compounds were measured on three different platforms. They may arguably be related to the effect of leptin on obesity and lipid metabolism
Glycerol: Measured on both Metabolon platforms (HD2 and HD4), glycerol can be linked to leptin via this JBC paper. The authors show that leptin increased glycerol release in adipocytes obtained from normal lean Zucker diabetic fatty rats (+/+). As glycerol forms the backbone of phospholipds, the association of leptin with these metabolites may possibly also be implicated in this process.

Click and focus on “insulin” (or use this link) to extend the network around leptin

Note the nice (partial correlation)-chain Leptin – Insulin – Pancreatic Hormone (PPY) – Glucagon, plus the (mutual best hit) association between PPY on the Somalogic platform and Hexose (H1) levels on the Biocrates platform.

Now we can ask: What associates with hexoses? by clicking on H1 (or following this link)

What we find are a number of molecules that are “orthologues” (mutal best hits) of hexose on other platforms, i.e. glucose in blood and urine measured on the Nightingale, Metablon and Chenomx platforms, and IgG-bound glycans on the two glycomics platform, and HbA1c from clinical biochemistry. The association with PLXNB2 on the Olink platform is not immediately evident and warrants further investigation.

Finally we can click and focus on HbA1c to arrive at the network displayed by comics at start-up

This network shall be discussed in a separate post – for now just note the link to diabetes and the association with TXNIP methylation, which is the strongest know EWAS for diabetes.