Salt Induces Adipogenesis/Lipogenesis and Inflammatory Adipocytokines Secretion in Adipocytes

Abstract

It is well known that high salt intake is associated with cardiovascular diseases including hypertension. However, the research on the mechanism of obesity due to high salt intake is rare. To evaluate the roles of salt on obesity prevalence, the gene expression of adipogenesis/lipogenesis and adipocytokines secretion according to adipocyte dysfunction were investigated in salt-loading adipocytes. High salt dose-dependently increased the expression of adipogenic/lipogenic genes, such as PPAR-γ, C/EBPα, SREBP1c, ACC, FAS, and aP2, but decreased the gene of lipolysis like AMPK, ultimately resulting in fat accumulation. With SIK-2 and Na+/K+-ATPase activation, salt increased the metabolites involved in the renin-angiotensin-aldosterone system (RAAS) such as ADD1, CYP11β2, and MCR. Increasing insulin dependent insulin receptor substrate (IRS)-signaling, resulting in the insulin resistance, mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and Akt-mTOR were activated but AMPK(Thr172) was depressed in salt-loading adipocytes. The expression of pro-inflammatory adipocytokines, TNFα, MCP-1, COX-2, IL-17A, IL-6, leptin, and leptin to adiponectin ratio (LAR) were dose-dependently increased by salt treatment. Using the inhibitors of MAPK/ERK, U0126, we found that the crosstalk among the signaling pathways of MAPK/ERK, Akt-mTOR, and the inflammatory adipogenesis can be the possible mechanism of salt-linked obesity. The possibilities of whether the defense mechanisms against high dose of intracellular salts provoke signaling for adipocytes differentiation or interact with surrounding tissues through other pathways will be explored in future research.

Higher Sodium Intake Assessed by 24 Hour Urinary Sodium Excretion Is Associated with Non-Alcoholic Fatty Liver Disease: The PREVEND Cohort Study

“…Furthermore, increased leptin concentrations have been described in animal studies in response to high sodium intake [39]. Indeed, high sodium induces lipogenesis and inflammatory adipocytokine secretion in adipocytes, which may provide a possible mechanism for inflammatory adipogenesis in sodium-linked obesity [41], and in turn may also play a role in accelerated NAFLD development [42]. On the other hand, in experimental animal models, the inhibition of the renin-angiotensin-aldosterone system reduces the activation of stellate and Kupffer cells and reduces oxidative stress possibly leading to the improvement of NAFLD [43].…”

Causal associations between urinary sodium with body mass, shape and composition: a Mendelian randomization study

“…Fonseca-Alaniz et al 47 observed that the high salt-induced adiposity in rats was characterized by high plasma leptin concentrations and adipocyte hypertrophy, which might be mediated by lipogenic capacity of white adipose mass. Lee et al 48 revealed that high salt increased the expression of adipogenic and lipogenic genes (such as PPAR-γ, SREBP1c, ACC, C/EBPα, and FAS), but decreased lipolysis gene expression (such as AMPK). However, its effect on lean mass requires more replications and mechanism research.…”

“…Lee et al . 48 revealed that high salt increased the expression of adipogenic and lipogenic genes (such as PPAR-γ, SREBP1c, ACC, C/EBPα, and FAS ), but decreased lipolysis gene expression (such as AMPK ). However, its effect on lean mass requires more replications and mechanism research.…”

Genes and Eating Preferences, Their Roles in Personalized Nutrition

“…The ADD1 gene encodes the structural protein of the cell (α-adducin), which is involved in the transport of sodium ions through kidneys [76]. The rs4961 polymorphism ( Figure 28) is associated with the disruption of sodium ion transport and salt-sensitive hypertension [77,78].…”