Resistin
Resistin was named for causing insulin “resistance” in mice, but in humans it’s produced by IMMUNE cells (macrophages), not fat cells — making it primarily an INFLAMMATORY marker. High resistin = active inflammation, associated with rheumatoid arthritis, cardiovascular disease, obesity, and metabolic syndrome. It links inflammation to metabolic dysfunction. Unlike mice, resistin doesn’t directly cause insulin resistance in humans but marks the inflammatory milieu contributing to it.
Resistin gets its name from its originally proposed function — “resistance” to insulin. While the story has become more complex in humans, resistin remains an important marker of inflammation and metabolic dysfunction. In humans, it’s produced primarily by immune cells (macrophages and monocytes), not fat cells as in mice, making it more of an inflammatory signal than a direct adipokine.
Why does this matter? Elevated resistin is associated with inflammation, insulin resistance, cardiovascular disease, and various chronic conditions. It may serve as a link between inflammation and metabolic dysfunction — helping explain why inflammatory conditions often coexist with diabetes and heart disease.
Resistin testing isn’t routine clinical practice but provides valuable insight in research settings and comprehensive metabolic evaluations. It helps characterize the inflammatory component of metabolic syndrome and may identify individuals at higher cardiometabolic risk.
Key Benefits of Testing
Resistin helps assess the inflammatory contribution to metabolic disease. As a marker linking inflammation with insulin resistance, it reveals aspects of metabolic dysfunction that glucose or lipids alone might miss.
In research and advanced metabolic profiling, resistin complements other adipokines (leptin, adiponectin) to provide a comprehensive picture of adipose tissue and immune system contributions to metabolic health.
What Does This Test Measure?
Resistin testing measures the concentration of this protein hormone in blood. While classified as an adipokine, in humans it primarily reflects immune cell activity rather than fat tissue function.
The Human vs. Mouse Difference
Understanding resistin requires recognizing an important species difference:
In mice: Resistin is produced mainly by fat cells and directly causes insulin resistance. It was named “resistin” because mouse studies showed it induced insulin resistance.
In humans: Resistin is produced primarily by macrophages and monocytes (immune cells), not adipocytes. Its role is more inflammatory than metabolic, though inflammation itself contributes to insulin resistance.
This difference explains some conflicting study results and why resistin’s role in human metabolic disease is more nuanced than originally proposed.
How Resistin Works in Humans
Production: Macrophages and monocytes are the main sources. Production increases with inflammatory stimuli like bacterial infection, inflammatory cytokines, and oxidative stress.
Actions:
- Pro-inflammatory — promotes inflammatory cytokine production
- Endothelial dysfunction — may impair blood vessel function
- Associated with insulin resistance — likely through inflammatory mechanisms
- May promote atherosclerosis
Resistin in the Adipokine Family
Comparing resistin to other adipokines:
Adiponectin: Protective. Higher is better. Anti-inflammatory.
Leptin: Satiety signal. High in obesity (with resistance). Mixed inflammatory effects.
Resistin: Inflammatory marker. High is generally unfavorable. Pro-inflammatory.
Why This Test Matters
Reflects Inflammatory Status
Elevated resistin indicates active inflammation, particularly from macrophages. It rises in infections, autoimmune diseases, and chronic inflammatory conditions. As a biomarker, it may capture inflammatory activity that other markers miss.
Links Inflammation to Metabolic Disease
The inflammation-insulin resistance connection is well established. Resistin may be one of the mediators — elevated resistin in inflammatory states contributes to the metabolic dysfunction seen with chronic inflammation.
Cardiovascular Risk Assessment
Higher resistin levels are associated with:
- Coronary artery disease
- Heart failure
- Atherosclerosis progression
- Cardiovascular events
Resistin may contribute to cardiovascular disease through promoting inflammation and endothelial dysfunction.
Evaluates Metabolic Syndrome
While the direct role of resistin in human insulin resistance is debated, elevated levels are consistently associated with metabolic syndrome components. It may mark the inflammatory milieu driving metabolic dysfunction.
Monitors Inflammatory Conditions
In rheumatoid arthritis, inflammatory bowel disease, and other chronic inflammatory conditions, resistin levels correlate with disease activity and may help assess response to treatment.
What Can Affect Your Resistin?
Causes of High Resistin
Inflammatory conditions:
- Rheumatoid arthritis — strongly elevated
- Systemic lupus erythematosus
- Inflammatory bowel disease
- Psoriasis
- Chronic infections
Obesity:
- Associated with higher resistin
- Likely due to adipose tissue macrophage infiltration
- Visceral obesity particularly associated
Type 2 diabetes:
- Often elevated, though relationship is complex
- May reflect inflammatory component of diabetes
Cardiovascular disease:
- Coronary artery disease
- Heart failure
- Acute coronary syndromes
Kidney disease:
- Impaired clearance raises levels
- Also increased production in uremic inflammation
Other conditions:
- Non-alcoholic fatty liver disease
- Sepsis and critical illness
- Some cancers
- Sleep apnea
Causes of Low Resistin
Lower inflammatory burden:
- Healthy individuals without inflammation
- Effective treatment of inflammatory conditions
Weight loss:
- May reduce resistin, likely through reducing macrophage infiltration
Certain medications:
- Anti-inflammatory drugs may lower resistin
- Thiazolidinediones (pioglitazone) may reduce levels
- Statins may have modest effect
Testing Considerations
Fasting: Generally recommended for consistency.
Acute illness: Active infection or acute inflammation will elevate resistin — may not reflect chronic status.
Kidney function: Impaired clearance in kidney disease raises levels independent of production.
Assay variability: Different assays may give different absolute values; use same lab for trending.
When Should You Get Tested?
Comprehensive Metabolic Assessment
When evaluating metabolic syndrome or unexplained insulin resistance, resistin as part of an adipokine panel provides information about inflammatory contribution.
Cardiovascular Risk Evaluation
For advanced cardiovascular risk assessment, particularly when inflammation is suspected to play a role, resistin may add prognostic information.
Inflammatory Disease Monitoring
In conditions like rheumatoid arthritis, resistin may help assess disease activity and treatment response.
Research Purposes
Studies examining the relationship between inflammation, obesity, and metabolic disease often include resistin as a biomarker.
Unexplained Inflammation
When evaluating chronic low-grade inflammation with unclear source, resistin contributes to the inflammatory profile.
Understanding Your Results
Resistin interpretation requires clinical context, particularly regarding inflammatory status:
General Interpretation
Lower resistin: Generally favorable. Suggests lower inflammatory burden and potentially better metabolic profile.
Higher resistin: Indicates active inflammation. Associated with increased cardiometabolic risk. May warrant investigation for inflammatory conditions if unexplained.
Context-Specific Interpretation
High resistin with known inflammatory disease: Expected. Reflects disease activity. Track trends with treatment.
High resistin with obesity: Suggests inflammatory adipose tissue dysfunction. Associated with higher metabolic risk. Target with weight loss and anti-inflammatory strategies.
High resistin with cardiovascular disease: May indicate inflammatory component contributing to atherosclerosis. Consider aggressive risk factor management.
High resistin without obvious cause: Consider subclinical inflammation, occult infection, or undiagnosed inflammatory condition. May warrant further evaluation.
Relationship with Other Markers
Resistin is best interpreted alongside:
- hs-CRP: Another inflammation marker — should correlate
- Adiponectin: Often inversely related — low adiponectin with high resistin suggests metabolic dysfunction
- Insulin/glucose: High resistin with insulin resistance supports inflammatory mechanism
What to Do About Abnormal Results
For High Resistin
Address underlying inflammation:
- Identify and treat inflammatory conditions
- Optimize management of autoimmune diseases
- Treat chronic infections
Lifestyle anti-inflammatory strategies:
- Weight loss — reduces adipose tissue inflammation
- Regular exercise — anti-inflammatory effects
- Anti-inflammatory diet — Mediterranean pattern, omega-3s
- Adequate sleep — sleep deprivation promotes inflammation
- Stress management — chronic stress increases inflammation
Address metabolic factors:
- Improve insulin sensitivity
- Optimize lipids
- Control blood pressure
- Manage blood glucose
Medications when indicated:
- Thiazolidinediones may lower resistin (for diabetes)
- Statins may have modest effect
- Disease-specific anti-inflammatory treatments
Monitor Response
Repeat resistin after sustained intervention (3-6 months) to assess improvement. Declining resistin with treatment suggests reduced inflammatory burden.
Related Health Conditions
Rheumatoid Arthritis
Strongly Elevated Resistin: Resistin is markedly elevated in RA and correlates with disease activity. It may contribute to the increased cardiovascular risk seen in RA. Effective RA treatment typically lowers resistin.
Cardiovascular Disease
Inflammation-Atherosclerosis Link: Elevated resistin is associated with coronary disease, heart failure, and cardiovascular events. It may promote atherosclerosis through endothelial dysfunction and inflammation.
Type 2 Diabetes
Inflammatory Component: While resistin doesn’t directly cause insulin resistance in humans as it does in mice, elevated levels mark the inflammatory milieu associated with diabetes.
Metabolic Syndrome
Inflammatory Marker: High resistin often accompanies metabolic syndrome, likely reflecting adipose tissue macrophage infiltration and chronic low-grade inflammation.
Chronic Kidney Disease
Elevated and Prognostic: Resistin is elevated in CKD due to reduced clearance and uremic inflammation. Higher levels may predict cardiovascular events in this population.
Why Regular Testing Matters
Resistin isn’t recommended for routine screening, but in appropriate contexts, trending levels provides insight into inflammatory burden and treatment response. For those with chronic inflammatory conditions or unexplained metabolic dysfunction, resistin adds valuable information to the clinical picture.
Related Biomarkers Often Tested Together
Adiponectin — Protective adipokine. Often inversely related to resistin. Low adiponectin with high resistin suggests metabolic dysfunction.
Leptin — Another adipokine. Completes the adipokine profile.
hs-CRP — Inflammation marker. Should correlate with resistin in inflammatory states.
IL-6 — Pro-inflammatory cytokine. Both elevated in inflammatory conditions.
TNF-alpha — Pro-inflammatory cytokine that stimulates resistin production.
Insulin — Insulin resistance assessment alongside resistin.
Note: Information provided in this article is for educational purposes and doesn’t replace personalized medical advice.
Frequently Asked Questions
Resistin is a protein originally named for its ability to cause insulin “resistance” in mice. In humans, it’s produced mainly by immune cells (macrophages) rather than fat cells, making it primarily an inflammatory marker associated with various chronic diseases.
The direct role is debated. Unlike in mice where resistin clearly causes insulin resistance, human resistin is produced by immune cells and likely contributes to insulin resistance indirectly through promoting inflammation. It’s more of a marker than a direct cause in humans.
High resistin indicates active inflammation, often from macrophages. It’s elevated in inflammatory conditions (rheumatoid arthritis, IBD), cardiovascular disease, obesity, and metabolic syndrome. It generally suggests an unfavorable inflammatory and metabolic profile.
While classified as an adipokine, human resistin is mainly produced by immune cells, not fat cells. Compare this to adiponectin (from fat cells, protective) and leptin (from fat cells, satiety signal). Resistin is primarily an inflammatory marker in humans.
Yes — treating underlying inflammatory conditions, weight loss, exercise, anti-inflammatory diet, and certain medications (thiazolidinediones, possibly statins) can reduce resistin levels.
Fasting is generally recommended for consistency, though resistin doesn’t fluctuate as dramatically with meals as glucose or insulin.
No — resistin isn’t part of standard clinical practice. It’s used in research settings and specialized metabolic evaluations. It may become more clinically useful as our understanding of its role in human disease evolves.
When used clinically, baseline testing followed by repeat after 3-6 months of intervention is reasonable. In research, testing frequency depends on study design.
References
Key Sources:
- Schwartz DR, Lazar MA. Human resistin: found in translation from mouse to man. Trends Endocrinol Metab. 2011;22(7):259-265.
- Patel L, et al. Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem Biophys Res Commun. 2003;300(2):472-476.
- Bokarewa M, et al. Resistin, an adipokine with potent proinflammatory properties. J Immunol. 2005;174(9):5789-5795.
