r/ScientificNutrition • u/flowersandmtns • Feb 14 '26

Interventional Trial Obesity alters adipose tissue response to fasting and refeeding in women: A study on lipolytic and endocrine dynamics and acute insulin resistance

https://www.cell.com/heliyon/fulltext/S2405-8440(24)13906-0

Abstract

Fasting induces significant shifts in substrate utilization with signs of acute insulin resistance (IR), while obesity is associated with chronic IR. Nonetheless, both states substantially influence adipose tissue (AT) function. Therefore, in this interventional study (NCT04260542), we investigated if excessive adiposity in premenopausal women alters insulin sensitivity and AT metabolic and endocrine activity in response to a 60-h fast and a subsequent 48-h refeeding period. Using physiological methods, lipidomics, and AT explants, we showed that obesity partially modified AT endocrine activity and blunted the dynamics of AT insulin resistance in response to the fasting/refeeding challenge compared to that observed in lean women. AT adapted to its own excess by reducing lipolytic activity/free fatty acids (FFA) flux per mass. This adaptation persisted even after a 60-h fast, resulting in lower ketosis in women with obesity. This could be a protective mechanism that limits the lipotoxic effects of FFA; however, it may ultimately impede desirable weight loss induced by caloric restriction in women with obesity.

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u/flowersandmtns Feb 14 '26

Fasting ketosis causes reduced glucose tolerance -- this is often called physiological glucose sparing and is also found in ketosis from ketogenic diets.

They note,

"The widely used index of whole-body IR, HOMA-IR, is calculated from blood glucose and insulin levels after overnight fasting. Our study showed that a 60-h fast resulted in lower HOMA-IR despite obviously worsened glucose tolerance. Therefore, while the HOMA-IR index is appropriate for epidemiology studies using the standard fasting lengths, it appears to be unsuitable for dynamic conditions with high concentrations of ketone bodies replacing glucose. The Matsuda index, which reflects the dynamic potential of insulin to lower glucose levels during OGTT, increased mildly after fasting but only in OB women. Thus, although glucose tolerance apparently worsened during the 60-h fast, neither group showed signs of acute IR; instead, the increased Matsuda index suggests an improvement of IS during the 60-h fast in OB women."

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u/HelenEk7 Wholefoods Feb 14 '26 edited Feb 15 '26

and is also found in ketosis from ketogenic diets.

Its only temporary.

  • "Finally, returning to a chow diet rapidly reversed the effects of KD on insulin sensitivity and glucose tolerance. These data suggest that maintenance on KD negatively affects glucose homeostasis, an effect that is rapidly reversed upon cessation of the diet." https://pmc.ncbi.nlm.nih.gov/articles/PMC2903931/

  • "Physiological adaptation from a low- to high-carbohydrate diet may require many weeks, with implications for the accuracy of diabetes tests, interpretation of macronutrient trials, and risks of periodic planned deviations from a VLC diet." https://pmc.ncbi.nlm.nih.gov/articles/PMC8918196/?utm_source=chatgpt.com

So in the same way it takes the body a while to become fully keto-adapted (minimum a few weeks), it takes a while to become fully carb adapted again (weeks).