Mendoza-Herrera · Frontiers in endocrinology 2021 · narrative review · n=?

The Leptin System and Diet: A Mini Review of the Current Evidence.

Cited 122 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review synthesizing animal and human literature without systematic review methodology.

PubMed 34899599 · doi:10.3389/fendo.2021.749050 · record verified 2026-08-29

What was done

The authors conducted a mini review of the animal and human literature examining how dietary patterns and macronutrient composition affect leptin signaling, leptinemia, and diet-induced leptin resistance in the context of obesity.

What was found

The abstract reports no numerical data. Diets high in fat, carbohydrates, fructose, or sucrose, and low in protein were identified as drivers of leptin resistance. Experimental evidence indicates that energy-restricted diets reduce circulating leptin in the short and long term and can potentially reverse leptin resistance in humans.

Why it matters

It highlights dietary modification—especially calorie restriction and macronutrient optimization—as a potential lifestyle approach to restore leptin sensitivity and assist in obesity management.

Limits

The review notes that the underlying literature suffers from limited rigor, small sample sizes, and substantial methodological heterogeneity. Clinically, there is no universally accepted definition or reliable method to measure leptin resistance in humans, and extreme very-low-energy diets are difficult to translate into sustainable clinical or population-wide practices.

Cited by