Table 1.

Identified connections between MDPs and CVD risk factors.

CVD Risk Factor	MDP	The Way of Action	References
Atherosclerosis	HNG	prevents CD36 and LOX-1 upregulation; upregulates the expression of ABCA1 and ABCG1	[34]
		suppress LOX-1 expression	[35]
		promotes autophagic degradation of Ox-LDL throughout lysosomal enzyme cathepsin D and its receptor FPRL1	[36]
	NH	induces the expression of KLF2;inhibits the high glucose-induced secretion of TNF-α and IL-1β; reduces the expression of VCAM-1 and E-selectin	[39]
	MOTS-c	decreases the expression levels of the AT-1 and ET-B receptors; increased the level of phosphorylated AMPK	[40]
Ageing	MOTS-c and HN	increase secretion of SASP components and rise mitochondrial respiration	[46]
		stimulate the secretion of SASP components (cytokines IL-1β, IL-6, IL-8, IL-10 and TNF-α)	[8]
Insulin resistance	HN	increases insulin sensitivity in muscles and the liver; increase fatty acid metabolism signalling and insulin-mediated AKT-signalling	[51,52]
	HNG	improves insulin sensitivity in the brain through the regulation of IRS-1/mTOR signalling pathway in the hippocampus	[53]
	SHLP2 and SHLP3	enhance 3T3-L1 pre-adipocyte differentiation	[4]
	SHLP2	SHLP2 increased glucose uptake and suppressed hepatic glucose production	[4]
	MOTS-c	increases fatty acids β-oxidation and mitochondria biogenesis; stimulates GLUT4 expression	[54,55]
Hyperlipidaemia	HN	decreases lipid accumulation and down-regulates lipogenesis genes (SREBP1, FAS and SCD1); enhances AMPK phosphorylation-mediated effect on IR; suppresses phosphorylation of the mTOR signalling pathway	[56]
	HNG	decreases liver triglyceride accumulation, visceral fat and body weight gain in high-fat diet-fed mice	[58]
	HNG and SHLP2	acting via the glutathione and sphingolipid metabolism pathways alter the concentrations of amino acid and lipid metabolites in plasma	[59]
	MOTS-c	increases AICAR levels and activates AMPK	[3]
		activates AMPK, GLUT4 and AC; stimulating mitochondria biogenesis and increasing the level of fatty acid β-oxidation	[60]
		improves mitochondria dynamics	[61]
		regulates expression of ARE and NFE2L2/NRF2	[21]