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HYPOTHESIS AND THEORY article

Front. Nutr.

Sec. Nutrition and Metabolism

Volume 12 - 2025 | doi: 10.3389/fnut.2025.1532961

This article is part of the Research Topic Dietary Patterns and Oxidative Stress: Implications for Obesity, T2D, and Cancer Management View all 5 articles

The energy model of insulin resistance: A unifying theory linking metabolic disease and cancer.

Provisionally accepted
  • 1 Other, Orlando, United States
  • 2 American Academy of Family Physicians, Leawood, Kansas, United States

The final, formatted version of the article will be published soon.

    The problem of insulin resistance has exploded in recent decades, from practically nonexistent in 1950 to nearly ubiquitous today. In spite of this, the dietary origins of insulin resistance remain elusive. Many have focused on the Western Diet, particularly saturated fat, as potentially causative agents. However, on a population level our consumption of saturated fat has remained unchanged while our consumption of polyunsaturated fats has increased more than 300%. This paper discusses the primary source of those polyunsaturated fatty acids (PUFA), a collection of eight chemically similar refined, bleached, and deodorized (RBD) seed oils, i.e. soy and canola, that now, together, represent the number one source of calories in the USA today, or approximately 30 percent of the average person's daily intake. The high PUFA content and low content of antioxidant protective factors, due to their removal during refining, bleaching, and deodorizing, foments the biochemical conditions for ongoing oxidation with resultant toxin formation during storage and cooking. This paper hypothesizes that RBD seed oil consumption promotes oxidative stress and may lead to insulin resistance. Specifically, cellular oxidative stress and hypoxia drive a shift to aerobic glycolysis as a fueling strategy known as the Warburg Effect, which has been observed in both cancerous cells and insulin-resistant cells. This may be a survival strategy to reduce cellular oxidative stress and protect mitochondria, the cell organelle most susceptible to oxidative stress. However, at the whole-organism level, increased cellular glucose utilization disrupts intravascular glucose homeostasis, ultimately causing the simultaneous elevation of both insulin and counterregulatory hormones. Competition between these the glucose-elevating and glucoselowering signals at the level of the hepatocyte leads to the phenotype of hepatic insulin resistance. In summary, the Energy Model of Insulin Resistance provides a framework for understanding that the primary metabolic deficit in people with insulin resistance may not be abnormal insulin signaling, but rather an abnormally increased metabolic demand for sugar. If correct, this would elucidate the mitochondrial origins of the Warburg Effect and it would suggest that avoiding RBD oils represents an important and understudied dietary strategy for addressing both insulin resistance and cancer.

    Keywords: Mitochondria, seed oil, PUFA, Oxidative Stress, Cancer, Insulin Resistance, Warburg effect, Obesity

    Received: 22 Nov 2024; Accepted: 31 Mar 2025.

    Copyright: © 2025 Shanahan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Catherine E Shanahan, Other, Orlando, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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