Resistin is a protein hormone, a cysteine-rich polypeptide of approximately 12.5 kDa, found circulating in both mouse and human serum. Classified as an adipokine, it is derived from adipose tissue, though its primary source varies between species. Resistin is involved in various physiological processes, making it a subject of ongoing research.
The Discovery and Naming of Resistin
Resistin was first identified in 2001 during a search for gene products within the fat cells of mice. Researchers observed that its expression was reduced by anti-diabetic medications called thiazolidinediones. The protein was named “resistin” because initial observations in these animal models suggested it caused “resistance to insulin.”
While resistin was initially characterized as being produced and released from adipose tissue in rodents, its primary source in humans differs significantly. In humans, resistin is mainly secreted by immune cells, specifically monocytes and macrophages, rather than fat cells. This distinction in cellular origin is important for understanding its physiological relevance and roles in human health.
The Role of Resistin in Metabolism
Resistin’s initial discovery highlighted its involvement in metabolic regulation, particularly its association with insulin resistance. Elevated levels of this protein are linked to the body’s diminished ability to respond effectively to insulin, a hormone that regulates blood sugar. This interference can lead to higher glucose concentrations in the bloodstream, as cells struggle to absorb sugar for energy.
Resistin contributes to insulin resistance by acting as an antagonist to insulin’s actions, especially in the liver. Studies in rodent models show that increased resistin levels decrease insulin sensitivity and alter glucose handling. Conversely, blocking resistin activity or genetically reducing its levels improves insulin sensitivity and restores glucose balance in these models.
This metabolic interference directly connects resistin to the development of conditions like obesity and type 2 diabetes. In individuals with type 2 diabetes and obesity, resistin levels are positively correlated with insulin resistance. This association suggests that resistin may play a part in how obesity progresses into insulin resistance, ultimately contributing to the onset of type 2 diabetes.
Resistin’s Connection to Inflammation
Beyond its metabolic associations, resistin also functions as a pro-inflammatory cytokine. This inflammatory role is attributed to its ability to activate intracellular pathways, such as the nuclear transcription factor-kappa B (NF-kB) pathway. Activation of this pathway stimulates the production of various inflammatory molecules, including interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α).
This inflammatory action contributes to its association with several chronic diseases, extending beyond metabolic disorders. Resistin’s involvement in inflammatory processes within blood vessels is particularly noted in cardiovascular diseases, such as atherosclerosis, which involves the hardening and narrowing of arteries. It can promote endothelial dysfunction and influence vascular remodeling, contributing to the progression of atherosclerosis.
Studies show that plasma resistin levels correlate with markers of inflammation and predict coronary atherosclerosis in humans, even independently of other inflammatory markers like C-reactive protein (CRP). This suggests resistin may link metabolic signals, inflammation, and the development of cardiovascular issues. Its ability to upregulate adhesion molecules on endothelial cells further supports its role in these inflammatory vascular processes.
Factors Influencing Resistin Levels
Several conditions and physiological states are associated with altered resistin levels. A primary factor is obesity, where increased body fat accumulation is linked to higher circulating resistin concentrations. This aligns with the understanding that adipose tissue, particularly in obese states, can release various adipokines, including resistin, which often have pro-inflammatory effects.
Chronic inflammatory states, such as those seen in rheumatoid arthritis or other systemic inflammatory conditions, are also associated with elevated resistin levels. Since resistin acts as a pro-inflammatory cytokine, its levels can rise in response to ongoing inflammation. This indicates a feedback loop where inflammation can increase resistin, and resistin can further promote inflammation.
Diet and lifestyle factors are being explored for their influence on resistin levels. For instance, diets rich in saturated fats may increase resistin levels, while those high in omega-3 fatty acids might lead to a reduction. Regular physical activity has been observed to decrease resistin levels, which could contribute to improved insulin sensitivity and reduced inflammation. These findings suggest that certain dietary patterns and lifestyle choices could modulate resistin concentrations, potentially impacting overall metabolic and inflammatory health.