Insulin itself is not the cause.
In response, the pancreas produces more insulin. That may hold blood glucose levels steady for a while, but it ultimately worsens fat storage and metabolic stress.
What causes insulin resistance?
The research cited here points to a chronic energy surplus: more energy coming in, over a long period, than the body can store safely (3, 6, 7). Insulin is often described as a blood sugar hormone, but its role in metabolism extends well beyond glucose.
At its core it is a hormone of energy excess: when you eat, particularly when you take in more energy than you need right then, insulin signals cells to take in nutrients, use what is required and store the rest for later.
Under normal conditions this system works remarkably well. Problems arise when excess energy intake persists over long periods and the body's capacity to store energy safely is overwhelmed.
Fat cells overload, fat spills into organs not designed to store it, and insulin signalling starts to fail.
How is fat storage linked to insulin resistance?
Healthy fat tissue keeps excess fat away from other organs, and insulin resistance follows when overloaded fat cells stop doing that job (3, 6, 7). White adipose tissue (body fat) is a highly active tissue designed to buffer excess energy safely.
Fat cells store energy mainly as triglycerides. They take in both glucose and free fatty acids from the blood, and glucose provides the glycerol needed to package fatty acids into triglycerides.
Insulin plays a central role: it increases glucose uptake, activates enzymes that promote fatty acid uptake and suppresses fat breakdown. In this way fat tissue acts as a metabolic buffer, and when it expands in a healthy way it supports normal metabolic function.
Fat cells run into trouble when they grow too large. Chronic overnutrition pushes existing fat cells beyond their optimal capacity.
The result is cellular stress and impaired function. This dysfunctional state is called adiposopathy, sometimes referred to as 'sick fat' (1).
Enlarged, dysfunctional fat cells tend to:
- become inflamed
- recruit immune cells such as macrophages
- release excess fatty acids into the bloodstream
Instead of storing energy safely, dysfunctional fat tissue leaks fat into circulation. That fat builds up in organs not designed to store it, including the liver and skeletal muscle.
Healthy fat tissue protects metabolic health, and once it becomes dysfunctional it drives disease.
How does fat in the liver and muscle interfere with insulin?
Fat that builds up in the liver and skeletal muscle disrupts insulin signalling and interferes with normal glucose metabolism (1, 2, 3). Fat stored anywhere outside fat tissue is known as ectopic fat.
Specific lipid intermediates, including ceramides and diacylglycerols, impair insulin's ability to stimulate glucose uptake and to suppress glucose production (4, 5).
After a meal, blood glucose rises and the pancreas releases insulin. Insulin binds to receptors on every cell type, including muscle cells and fat cells, and triggers signals inside the cell that move glucose transporters, mainly GLUT4, to the cell surface.
GLUT4 acts as a gateway that lets glucose in from the blood. In muscle, that glucose is used for energy or stored as glycogen; in fat tissue, it helps build and store triglycerides.
When insulin signalling is intact, glucose is cleared from the blood and distributed where it is needed.
When ectopic fat impairs that signal, muscle takes up less glucose, the liver produces excess glucose and fat breakdown increases even with insulin present. That state is insulin resistance.
Can insulin resistance be reversed?
Insulin resistance is highly responsive to lifestyle change. Insulin sensitivity can be restored by improving diet quality, reducing excess energy intake and engaging in regular physical activity.
Three strategies are particularly effective: reducing carbohydrate intake, reducing total energy intake and increasing physical activity.
What does eating fewer carbohydrates do for insulin resistance?
Lowering carbohydrate intake reduces how much glucose enters the bloodstream and decreases the demand for insulin. Less insulin exposure makes it easier for the body to mobilise stored fat and limits further build-up of ectopic fat.
This approach can be especially beneficial for people with established insulin resistance.
Does losing weight improve insulin sensitivity?
It can. Even a modest loss of 3 to 5% of body weight can significantly reduce liver fat and improve insulin sensitivity in specific tissues (8).
For someone who weighs 90 kg, that is a loss of only 2.7 to 4.5 kg. This is very achievable for most people.
Total energy intake matters as well as carbohydrate. Eating fewer calories leads to smaller fat cells, less inflammation and improved insulin signalling.
What is the best exercise for insulin resistance?
Both aerobic exercise and resistance training improve insulin sensitivity, and combining the two provides the greatest benefit. Exercise works through more than one route.
Insulin normally moves GLUT4 to the surface of muscle cells, but muscle contraction activates the same pathway independently of insulin. This insulin-independent glucose uptake lets glucose into muscle even when insulin signalling is impaired.
Regular physical activity also reduces liver fat, improves mitochondrial function and increases fat oxidation in skeletal muscle. Read more in The Hidden Metabolic Benefits of Exercise.
Frequently asked questions
What is insulin resistance?
Insulin resistance is when insulin's signal stops working well. Muscle takes up less glucose, the liver produces excess glucose and fat breakdown increases even with insulin present.
The pancreas compensates by producing more insulin, which may hold blood glucose for a while but ultimately worsens fat storage and metabolic stress.
What is the main reason for insulin resistance?
In the research this article cites, a chronic energy surplus. When fat tissue can no longer store the surplus safely, fat spills into the liver, muscle and other organs and impairs insulin signalling.
Insulin itself is not the cause: it is an essential hormone that helps the body manage energy.
What happens to insulin resistance at the cellular level?
Fat builds up in muscle and the liver, and lipid intermediates such as ceramides and diacylglycerols impair insulin's signal. That signal normally moves GLUT4 glucose transporters to the cell surface to let glucose in.
When it is impaired, muscle takes up less glucose and the liver produces excess glucose.
Does body fat cause insulin resistance?
Not while fat tissue is healthy: it buffers surplus energy and keeps excess fat away from other organs. Trouble starts when chronic overnutrition enlarges fat cells beyond capacity.
They become inflamed and leak fat into the blood; it builds up in the liver and muscle and disrupts insulin signalling.
Can insulin resistance go back to normal?
Insulin resistance is highly responsive to lifestyle change. Insulin sensitivity can be restored by improving diet quality, reducing excess energy intake and engaging in regular physical activity.
Three strategies are particularly effective: reducing carbohydrate intake, reducing total energy intake and increasing physical activity.
Does eating fewer carbs help with insulin resistance?
Lowering carbohydrate intake reduces how much glucose enters the bloodstream and decreases the demand for insulin. Less insulin exposure makes it easier to mobilise stored fat and limits further build-up of fat in the liver and muscle.
This approach can be especially beneficial for people with established insulin resistance.
Does eating fewer calories help with insulin resistance?
It can. Total energy intake matters as well as carbohydrate: eating fewer calories leads to smaller fat cells, less inflammation and improved insulin signalling.
What is the best exercise for insulin resistance?
Both aerobic exercise and resistance training improve insulin sensitivity, and combining the two provides the greatest benefit. Muscle contraction moves GLUT4 to the cell surface without needing insulin, so glucose can enter muscle even when insulin signalling is impaired.
Regular activity also reduces liver fat.
Sources
- Samuel VT, Shulman GI. The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux. J Clin Invest. 2016;126(1). https://doi.org/10.1172/JCI77812
- Petersen MC, Shulman GI. Mechanisms of insulin action and insulin resistance. Physiol Rev. 2018;98(4). https://doi.org/10.1152/physrev.00063.2017
- Lewis GF, Carpentier A, Adeli K, Giacca A. Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr Rev. 2002;23(2). https://doi.org/10.1210/edrv.23.2.0461
- Kojta I, Chacińska M, Błachnio-Zabielska AU. Obesity, bioactive lipids, and adipose tissue inflammation in insulin resistance. Nutrients. 2020;12(5). https://doi.org/10.3390/nu12051305
- Sokołowska E, Błachnio-Zabielska AU. The role of ceramides in insulin resistance. Front Endocrinol. 2019;10. https://doi.org/10.3389/fendo.2019.00577
- Gustafson B, Hedjazifar S, Gogg S, Hammarstedt A, Smith U. Insulin resistance and impaired adipogenesis. Trends Endocrinol Metab. 2015;26(4). https://doi.org/10.1016/j.tem.2015.01.006
- Lee SH, Park SY, Choi CS. Insulin resistance: from mechanisms to therapeutic strategies. Diabetes Metab J. 2021;46(1). https://doi.org/10.4093/dmj.2021.0280
- Pang MD, Bastings JJAJ, Op den Kamp-Bruls YMH, et al. The effect of weight loss on whole-body and tissue-specific insulin sensitivity and hepatic lipid content and composition: SWEET substudy. Obesity. 2023;31(7):1745-1754. https://doi.org/10.1002/oby.23773
This article is for informational and educational purposes only. It is not, nor is it intended to be, a substitute for professional medical advice, diagnosis or treatment, and should never be relied upon for specific medical advice.
