Very low-density lipoprotein and the human health

Table 1 Nuclear magnetic resonance-based very low-density lipoprotein classification

Classes	Associated impact	Ref.
Small VLDL	Metabolically fit individuals with smaller (below medium) VLDL size	[9]
Largest VLDL (including chylomicrons) and five different VLDL subclasses	The level of all lipid components in the VLDL subclasses was enhanced as glucose tolerance was reduced	[10]
Large and intermediate VLDL	Progressive insulin resistance was associated with enhanced VLDL size and an enhancement in large VLDL particles	[11]

VLDL: Very low-density lipoprotein.

Table 2 Summary of endocrinology effect on very low-density lipoprotein

Disorder/syndrome	Impact due to VLDL	Ref.
Cushing syndrome	Enhanced production	[61]
Exogenous cortisol	Decrease in degradation and enhanced adipose lipolysis	[62]
Aldosterone	Stimulation of aldosterone secretion	[65-67]
Growth hormone deficiency	Enhanced secretion and decline in clearance	[61]
Growth hormone treatment	Increased adipose lipolysis and increased clearance	[61]
Hypothyroidism	Decreased degradation with enhanced secretion	[73,74]
Androgen	Androgen-deprivation treatment: Enhanced concentration; transgender males with testosterone treatment: Enhanced concentration	[80-82]
Polycystic ovary syndrome	Enhanced concentration	[84]
Estrogen/progesterone therapy	Enhanced concentration	[85,86]
Prolactinoma	Uncertain	[94-96]

VLDL: Very low-density lipoprotein.

Table 3 Cancer types where experimental evidence directly implicates very low-density lipoprotein/very low-density lipoprotein receptor in experimental models

Cancer type	Model evidence	Mechanistic insight
HCC	shRNA knockdown reduces proliferation in hepatoma cells	VLDLR supports tumor cell growth
ccRCC	siRNA knockdown reduces lipid uptake in RCC cells	VLDLR mediates pathological lipid uptake
Breast cancer	VLDLR manipulation alters cancer cell behavior; VLDL increases metastasis in vivo	VLDLR/VLDL enhance tumor aggressiveness
Gastrointestinal cancer	Altered VLDLR subtype expression in tumor cell lines/tissues	Suggests involvement in differentiation but not fully functional yet
Colorectal cancer	Altered expression correlates with tumor features	Functional causality still emerging

HCC: Hepatocellular carcinoma; ccRCC: Clear-cell renal cell carcinoma; VLDLR: Very low-density lipoprotein receptor; VLDL: Very low-density lipoprotein.

Table 4 Mechanistic links demonstrated in vitro and in vivo for breast cancer and hepatocellular carcinoma

Feature	Breast cancer	Hepatocellular carcinoma
Primary role of VLDL	External lipid fuel for growth and metastasis	External lipid source supporting survival
Key receptors	CD36, VLDLR	VLDLR
Hypoxia involvement	Indirect (metabolic stress adaptation)	Direct via HIF-1α to VLDLR
Demonstrated outcomes	Increased metastasis, invasion, stemness	Increased proliferation, survival
Experimental proof	Cell culture + mouse metastasis models	Cell culture + hypoxia models

VLDL: Very low-density lipoprotein; VLDLR: Very low-density lipoprotein receptor; HIF: Hypoxia-inducible factor.

Table 5 Mechanistic hypothesis in other cancers

Cancer type	Evidence type	Strength of causality
Breast cancer	In vitro + in vivo functional studies	Strong (mechanistic)
Hepatocellular carcinoma	In vitro + hypoxia-driven mechanistic studies	Strong (mechanistic)
Oral/HNSCC	Expression + serum lipid correlations	Weak (associative)
Ovarian cancer	Clinical correlations + expression data	Weak-moderate (associative)
Pancreatic cancer	Indirect metabolic inference	Speculative (hypothesis)

HNSCC: Head and neck squamous cell carcinoma.