Research shows FGF19 enhances energy expenditure and thermogenesis in mice — Evidence Review
Published in American Journal of Physiology -- Endocrinology and Metabolism, by researchers from Obesity and Comorbidities Research Center (OCRC), State University of Campinas (UNICAMP)
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Table of Contents
Researchers have shown that the gut-derived hormone FGF19 can signal to the brain’s hypothalamus to increase energy expenditure and promote fat burning in obese mice; related studies generally support these findings and highlight FGF19’s broader metabolic benefits (original source).
- Several earlier studies have found that FGF19 increases metabolic rate, reduces weight gain, and improves glucose metabolism in mice, with effects on both brown and white adipose tissue and the liver, supporting the new study’s conclusions 1 2 5.
- The new findings that FGF19 acts specifically via the hypothalamus to regulate thermogenesis and energy homeostasis build upon prior evidence that FGF19 and related hormones influence energy balance through both central and peripheral mechanisms 2 4 5.
- Some research suggests FGF19’s anti-obesity effects may not depend solely on thermogenic pathways, indicating that multiple mechanisms—including reduced lipid absorption and modulation of bile acid synthesis—may contribute to its metabolic actions 13.
Study Overview and Key Findings
Obesity and metabolic diseases remain major global health challenges, with current treatments often providing limited or temporary benefits. This study addresses the urgent need for novel therapeutic approaches by investigating FGF19, a hormone produced in the intestine, and its ability to influence energy metabolism through direct actions in the brain. By focusing on FGF19's role in the hypothalamus—a brain region crucial for energy balance and thermoregulation—the research advances our understanding of gut-brain signaling and its potential for obesity intervention.
| Property | Value |
|---|---|
| Organization | Obesity and Comorbidities Research Center (OCRC), State University of Campinas (UNICAMP) |
| Journal Name | American Journal of Physiology -- Endocrinology and Metabolism |
| Authors | Lucas Zangerolamo, Helena Cristina de Lima Barbosa, Yu-Hua Tseng |
| Population | Mice |
| Methods | Animal Study |
| Outcome | Energy expenditure, appetite control, thermogenesis |
| Results | FGF19 improved energy homeostasis and thermogenesis in mice. |
The study found that administering FGF19 directly to the brains of obese mice activated hypothalamic pathways that increased the activity of thermogenic adipocytes—fat cells that burn energy to produce heat. This process enhanced energy expenditure, promoted the use of stored fat, improved blood glucose control, lowered peripheral inflammation, and increased cold tolerance. The beneficial effects depended on an intact sympathetic nervous system and were associated with increased expression of FGF19 receptors in the hypothalamus, suggesting a direct role in coordinating energy balance and thermoregulation.
Literature Review: Related Studies
To place these findings in context, we searched the Consensus research database, which includes over 200 million scientific papers. We used the following search queries to identify related studies on FGF19, energy metabolism, and thermogenesis:
- FGF19 energy homeostasis thermogenesis
- natural hormones fat burning mechanisms
- mice studies FGF19 weight loss effects
Related Studies Table
| Topic | Key Findings |
|---|---|
| How does FGF19 influence energy expenditure and thermogenesis? | - FGF19 administration increases metabolic rate and activates brown adipose tissue, reducing weight gain in obese mice without decreasing food intake 1 5. - Both FGF19 and FGF21 promote energy expenditure and correct glucose imbalance, with overlapping metabolic effects in vivo 2 5. |
| What mechanisms mediate the anti-obesity effects of FGF19 and related hormones? | - FGF19’s anti-obesity effects may not require UCP1-dependent thermogenesis but are linked to decreased bile acid synthesis and reduced dietary lipid absorption 13. - The FGF family (including FGF19, FGF21, FGF1) regulates energy homeostasis via central and peripheral pathways, acting on liver, adipose tissue, and the brain 4 5. |
| How do other natural hormones regulate fat metabolism and thermogenesis? | - Thyroid hormones and ovarian hormones also increase thermogenesis and energy expenditure, with thyroid hormones inducing browning of white adipose tissue through central (hypothalamic) mechanisms 6 8 10. - Testosterone regulates fat distribution and metabolism, improving insulin sensitivity and reducing adiposity in deficient males 9. |
| What are other metabolic roles and therapeutic potentials of FGF19? | - FGF19 protects against muscle wasting, improves skeletal muscle mass, and ameliorates metabolic complications in obesity and chronic disease models 11 12 14. - FGF19 and FGF21 share similar metabolic effects but differ in hepatic proliferation and receptor interactions; targeting FGF pathways may offer new therapies for metabolic disease 2 4 5. |
How does FGF19 influence energy expenditure and thermogenesis?
Multiple animal studies have demonstrated that FGF19 increases metabolic rate, promotes the activation of thermogenic fat cells, and reduces weight gain in obese mice. The new study extends this knowledge by pinpointing the hypothalamus as a critical brain region mediating these effects, thereby strengthening the evidence that FGF19 acts centrally as well as peripherally.
- FGF19 increases oxygen consumption and activates brown adipose tissue, leading to greater fat oxidation and reduced adiposity independent of food intake 1 5.
- FGF19 and related hormone FGF21 both enhance energy expenditure and improve glucose and lipid metabolism in obese mice 2 5.
- The current study’s focus on hypothalamic signaling aligns with data showing central pathways are necessary for full thermogenic response 10.
- The beneficial effects of FGF19 on energy balance have been observed across different models of obesity and metabolic disease 1 2 5.
What mechanisms mediate the anti-obesity effects of FGF19 and related hormones?
FGF19’s anti-obesity actions are multifaceted, involving both increased energy expenditure and other mechanisms such as reduced dietary lipid absorption. While the new study emphasizes hypothalamic-induced thermogenesis, related research suggests that FGF19 can also lower body weight through decreased bile acid synthesis and impacts on fat absorption.
- The anti-obesity effects of FGF19 are not solely dependent on UCP1-mediated thermogenesis; inhibition of bile acid synthesis and reduced lipid absorption contribute significantly 13.
- FGF family hormones act on multiple tissues, including the central nervous system and liver, to coordinate energy metabolism 4 5.
- FGF19’s central and peripheral actions may complement each other, with the hypothalamic pathway being particularly relevant for thermoregulation 4 10.
- Understanding these mechanisms is critical for developing targeted obesity therapies with minimal side effects 4 13.
How do other natural hormones regulate fat metabolism and thermogenesis?
Other hormones, such as thyroid, ovarian, and sex steroids, also regulate energy balance through central and peripheral mechanisms. These findings contextualize FGF19’s actions within a broader landscape of hormonal regulation of metabolism, thermogenesis, and fat distribution.
- Thyroid hormones stimulate both obligatory and facultative thermogenesis, acting centrally to induce browning of white fat and activate brown adipose tissue 6 10.
- Ovarian hormones impact appetite, fat distribution, and energy expenditure, with estrogen promoting leanness and metabolic health in females 8.
- Testosterone influences body composition and metabolic health, particularly in men with deficiency 9.
- These hormones, like FGF19, often exert their effects through the sympathetic nervous system and hypothalamic circuits 6 8 10.
What are other metabolic roles and therapeutic potentials of FGF19?
Beyond its effects on adipose tissue, FGF19 has been shown to protect against muscle wasting, improve skeletal muscle mass, and ameliorate metabolic disturbances in models of obesity and chronic disease. These broader actions underscore FGF19’s promise as a therapeutic target.
- FGF19 treatment increases muscle fiber size, improves strength, and protects against obesity-induced muscle atrophy, partly through the AMPK/SIRT1/PGC-1α signaling pathway 11 12 14.
- The hormone improves glucose tolerance and reduces liver inflammation in chronic kidney disease and obese mice 12 14.
- FGF19 and FGF21 share similar metabolic effects, though differ in some tissue-specific actions and receptor interactions 2 4 5.
- The potential for FGF-based therapies extends to conditions such as sarcopenic obesity and metabolic syndrome 11 12 14.
Future Research Questions
While recent studies have advanced our understanding of FGF19’s metabolic actions, several important questions remain. Further research is needed to clarify the precise mechanisms of FGF19’s central and peripheral effects, evaluate long-term safety and efficacy in humans, and explore how these findings translate from animal models to clinical application.
| Research Question | Relevance |
|---|---|
| What are the long-term effects of FGF19-based therapies on energy expenditure and metabolic health in humans? | Most evidence comes from animal studies; human trials are needed to assess safety, efficacy, and sustainability of FGF19-based interventions for obesity and metabolic disease 1 2 5. |
| How does central FGF19 signaling in the hypothalamus interact with other hormonal and neural pathways regulating energy homeostasis? | Understanding interactions with thyroid, ovarian, and other hormones will clarify FGF19’s full metabolic impact and potential combinatorial therapies 4 6 8 10. |
| What are the mechanisms by which FGF19 reduces inflammation and improves cold tolerance? | The observed reduction in inflammation and improved cold tolerance suggest additional pathways beyond thermogenesis may be involved, warranting further mechanistic investigation 11 12 14. |
| Can FGF19 analogs or agonists be safely developed to target the hypothalamus in humans? | Direct hypothalamic targeting may maximize therapeutic benefits, but delivery methods and safety profiles must be established in clinical studies 4 5 13. |
| How does FGF19 signaling influence skeletal muscle function and sarcopenic obesity? | FGF19’s effects on muscle mass and function could expand its therapeutic potential to conditions like sarcopenic obesity and muscle wasting disorders 11 12 14. |
This comprehensive analysis highlights the robust and multifaceted nature of FGF19’s metabolic actions, the central role of hypothalamic signaling, and the need for further research to translate these findings into effective therapies for obesity and related disorders.