Protein2026-06

High protein ingestion does not affect whole-body insulin sensitivity in individuals with overweight or obesity.

Ancu Oana, Hauge-Evans Astrid C, Draicchio Fulvia, Neculescu Diana-Elena et al. — Journal of the Endocrine Society

Summary

A study investigated whether eating a lot of protein affects how the body uses insulin in people who are overweight or obese. It found that while high protein intake didn't change overall body-wide insulin sensitivity, it did cause some beneficial changes in insulin-related signals within muscle cells. This suggests potential cellular-level effects that don't immediately translate to whole-body improvements.

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Key points

High protein intake was studied in individuals who were overweight or obese.
It did not improve how their bodies used insulin overall.
However, some internal cell signals related to insulin action showed positive changes.
These cellular changes did not lead to a measurable improvement in whole-body insulin sensitivity.

What the study looked at

Researchers investigated whether consuming high amounts of protein could influence how the body responds to insulin in individuals who are overweight or obese. They also explored if such diets altered specific molecular signals within muscle and fat cells that are involved in insulin action. The study involved two main approaches. In an acute phase, participants consumed different protein meals, and muscle biopsies were taken to observe immediate cellular changes. In a longer, 18-week phase, a subset of participants followed either a high-protein diet or a control diet, with overall insulin sensitivity measured and fat tissue samples analyzed. All participants were overweight or obese. The study concluded that neither a single high-protein meal nor an 18-week high-protein diet improved overall body-wide insulin sensitivity in these individuals. However, after an acute high-protein meal, some key proteins involved in insulin signaling within muscle cells showed changes that could be considered beneficial. These findings suggest potential positive effects at a very basic cellular level, even if they didn't translate into a measurable improvement in how the whole body uses insulin.

Dietary takeaway

This research suggests that for individuals who are overweight or obese, simply increasing protein intake might not directly improve how their body uses insulin on a whole-body level. While there were hints of positive changes in cellular signaling, these didn't lead to a measurable overall improvement. Therefore, while protein is a vital nutrient, this single study does not definitively support high-protein diets as a primary strategy for enhancing whole-body insulin sensitivity, and more research is needed to understand these complex interactions.

Abstract

CONTEXT: High protein diets (HPD), rich in branched-chain amino acids (BCAAs), are proposed to enhance glycemic control. The metabolic implications of elevated BCAAs in insulin resistance (IR) are unclear, but overactivation of ribosomal protein S6 kinase B1 (S6K1)-related signaling pathway may contribute to IR. OBJECTIVE: To investigate the impact of 2 dietary protein interventions on IR and molecular signaling in skeletal muscle (acutely) and adipose tissue (18-week period) in overweight/obese individuals. METHODS: The acute study included ingestion of 50 g protein (MPD), 100 g protein (HPD), or 50 g of protein with added fat (MPDAF) on 3 different occasions with muscle biopsies before and after. The 18-week analysis used a subset of data with available adipose tissue biopsies from a randomized, controlled, isoenergetic dietary intervention, focusing on the relevant HPD and control diets. Insulin sensitivity was assessed using labeled intravenous glucose tolerance tests acutely, and by euglycemic-hyperinsulinemic clamp in the 18-week intervention. RESULTS: Inositol hexakisphosphate kinase 1 (IP6K1) and total AMP-activated protein kinase (AMPK) protein content significantly decreased following the HPD meal ( = .048 and = .006 respectively), alongside increased -AktThr/Akt2 ( = .046), while S6K1 mRNA was lower after 6 weeks of HPD, compared to the control diet group ( = .046), but not at 18 weeks. However, neither intervention changed whole-body IR. CONCLUSION: Key proteins implicated in intracellular insulin signaling were altered with an acute HPD meal (decreased IP6K1 and AMPK, increased pAkt/Akt2 activity), indicating potential enhancement of insulin-mediated glucose signaling at the molecular level. These findings suggest that, while systemic IR was unchanged, high protein intake may have beneficial effects on cellular insulin signaling.

View on PubMed →DOI: 10.1210/jendso/bvag013