ReviewObesity (Silver Spring, Md.)2022
Beyond appetite regulation: Targeting energy expenditure, fat oxidation, and lean mass preservation for sustainable weight loss.
Review in Obesity (Silver Spring, Md.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
68 citing papers in PubMed, 3 syntheses or guidelines pooled it, 120 citations in OpenAlex.
- Attenuation of Adaptive Thermogenesis by a Culinary Dose of Red Pepper During 24-Hour Negative Energy Balance.Nutrition reviews · 2026Pooled it
- Proposed Definitions and Clinical Recommendations for the Management of Weight Recurrence, Partial Response, and Nonresponse Following Metabolic and Bariatric Surgery.Obesity surgery · 2025Pooled it
- Efficacy and safety of ephedra-containing oral medications: a systematic review, meta-analysis, and exploratory dose-response analysis for weight reduction.Frontiers in pharmacology · 2024Pooled it
- Metabolically Guided Walking and Plant-Based Nutrition Enhance Body Composition and Weight Loss.International journal of environmental research and public health · 2026Trial
- Trial
- GDF8 and activin A are the key negative regulators of muscle mass in postmenopausal females: a randomized phase I trial.Nature communications · 2025Trial
- Glucagon-like peptide-1/glucagon receptor agonism associates with reduced metabolic adaptation and higher fat oxidation: A randomized trial.Obesity (Silver Spring, Md.) · 2023Trial
- A multi-functional oral small molecule targeting energy and lipid metabolism to treat obesity and related metabolic disorders.Science advances · 2026Article
- Defining Healthy Weight Loss and Target Weight in the Era of Highly Effective Treatment of Patients With Obesity.Journal of cachexia, sarcopenia and muscle · 2026Review
- The evolving landscape of obesity pharmacotherapy.Nature reviews. Drug discovery · 2026Review
- Structurally defining neurokinin selectivity to improve NK2R agonists.Nature structural & molecular biology · 2026Article
- Multidisciplinary Therapy to Target Obesity and Its Complications in Adult Population: A Narrative Review.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026Review
- GPR75 genetic manipulations in mice reveal central mechanism for weight loss independent of developmental effects.Molecular metabolism · 2026Article
- Adissp activates insulin-independent glucose disposal and energy expenditure in white fat to treat diabetes and cardiometabolic disease.Science advances · 2026Article
- From Lipids to Mitochondria: Shared Metabolic Alterations in Obesity and Alzheimer's Disease.Cells · 2026Review
- Physiological interplay among obesity, male fertility, and aryl hydrocarbon receptor in human and mice: A mini review.Open veterinary journal · 2026Review
- Cardiometabolic Gains Unrelated to Weight Loss-Adjusted Body Fat or Distribution Changes in Adults With and Without Diabetes.Obesity (Silver Spring, Md.) · 2026Article
- Pharmacological intervention: Challenges and promising outcomes for fat loss and preservation of lean body mass in the treatment of overweight and type 2 diabetes.Diabetes, obesity & metabolism · 2026Review
- Mitochondria as a Therapeutic Target in Metabolic Disorders.Mini reviews in medicinal chemistry · 2026Review
- Impact of Semaglutide on fat mass, lean mass and muscle function in patients with obesity: The SEMALEAN study.Diabetes, obesity & metabolism · 2026Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
New appetite-regulating antiobesity treatments such as semaglutide and agents under investigation such as tirzepatide show promise in achieving weight loss of 15% or more. Energy expenditure, fat oxidation, and lean mass preservation are important determinants of weight loss and weight-loss maintenance beyond appetite regulation. This review discusses prior failures in clinical development of weight-loss drugs targeting energy expenditure and explores novel strategies for targeting energy expenditure: mitochondrial proton leak, uncoupling, dynamics, and biogenesis; futile calcium and substrate cycling; leptin for weight maintenance; increased sympathetic nervous system activity; and browning of white fat. Relevant targets for preserving lean mass are also reviewed: growth hormone, activin type II receptor inhibition, and urocortin 2 and 3. We endorse moderate modulation of energy expenditure and preservation of lean mass in combination with efficient appetite reduction as a means of obtaining a significant, safe, and long-lasting weight loss. Furthermore, we suggest that the regulatory guidelines should be revisited to focus more on the quality of weight loss and its maintenance rather than the absolute weight loss. Commitment to this research focus both from a scientific and from a regulatory point of view could signal the beginning of the next era in obesity therapies.
Indexed as
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.