Table 1 Systemic, tissue and cellular molecular correlates of WC

System

Endocrine system

Adaptive response to fat recovery and more difficult weight loss;

increase in postprandial blood glucose;

increased risk of diabetes

[22,23,24,25]

Circulatory system

An increase in blood pressure;

deterioration of blood lipid levels in women;

increased risk of fatty liver

[26,27,28,29,30]

Intestinal barrier

Disruption of the intestinal barrier, including inhibition of mucus production, weakening of tight junctions, changes in the structure of the intestinal villi and intestinal inflammation;

enlargement of the intestinal absorption area;

increased secretion of pro-inflammatory cytokines in the gastrointestinal tract and down-regulation of intestinal immune defences;

increased distribution of bacteria in the intestinal flora and leakage of pathogenic components and metabolites through the intestinal lumen;

leakage of lipopolysaccharides and other toxins into the blood, causing metabolic endotoxaemia

[31,32,33,34,35,36, 39,40,41,42,43,44]

Tissue

Adipose tissue

More pronounced proliferation of preadipocytes;

increased volume and number of adipocytes and accumulation of fat;

increased adipose tissue cell pressure

[54, 59,60,61,62,63, 65,66,67]

Skeletal muscle

Ectopic aggregation of lipids in skeletal muscle and formation of perimuscular adipose tissue; loss of muscle mass; decreased uptake of glucose transporter protein 4 (GLUT4); inhibition of mitochondrial function and increased formation of reactive oxygen species

[70,71,72,73,74,75,76,77,78,79,80]

Cellular and Molecular

Immune cells

Immune cell accumulation: B cells are the first to accumulate in adipose tissue and have a significant inflammatory-promoting effect on adipose tissue expansion, releasing IL-6 and interferon; subsequently the number of CD4 + and CD8 + T cells increases T cells; the number of macrophages gradually increases, IL-6 and TNF-α secretion increases, and the increase in circulating glucose and fatty acid substrates, lipotoxicity and tissue hypoxia, causing M1 macrophage polarization that persists

[85,86,87,88,89, 93, 97]

Molecular Mechanisms

1. Immune cell activation: blockade of RIPK1 increases iNKT cell activity; a mixture of palmitic acid or long-chain fatty acids increases the expression of pro-inflammatory molecules in macrophages and induces M1 polarization through the involvement of TLR2 and TLR4 and activation of the JNK pathway; induces activation of the NLRP3 inflammasome, promotes maturation and secretion of IL-1β and IL-18, triggers oxidative stress and inflammatory response; Lmot4-resistin signaling presents adipose tissue and liver crosstalk

[53, 98,99,100,101,102, 104, 106, 111, 112, 115,116,117, 119, 121, 124, 125]

2. Oxidative stress: adverse effects on 5-OHmU levels and significant oxidative damage; stimulation of the HIF-1 pathway triggers lactate accumulation and local inflammation; increased ROS levels and activation of metabolic inflammation

3. Adipokines: affects adipokine levels and affects macrophage polarization; decreased expression of lipocalin and resistin; dysregulated expression of CTRP3 causes increased inflammation and induces metabolic dysfunction; leptin promotes the release of pro-inflammatory cytokines; decreased serum leptin levels; increased levels of resistin and upregulated expression of stat3-activated IL-1β, IL-6 and IL-8; Lower levels of adiponectin stimulate macrophage inflammation