Introduction
Obesity is a growing global health concern, not only for humans but also for animals, particularly those living in close proximity to human populations. This article examines a research study on the use of Fibroblast Growth Factor 21 (FGF21) to combat obesity in rhesus macaque monkeys, along with a real-world example of an obese monkey named "Uncle Fat" undergoing a weight loss program. By combining scientific research with a case study, we aim to provide a comprehensive understanding of the challenges and potential solutions for managing obesity in primates.
FGF21 and Weight Loss in Obese Rhesus Macaques
Background on FGF21
Fibroblast growth factor 21 (FGF21) is a hormone that belongs to the FGF19 subgroup of endocrine FGFs. It is primarily expressed in the liver and secreted from there. FGF21 has been identified as a key metabolic regulator. Its metabolic actions are mediated through receptors in adipose tissue and the central nervous system (CNS). Since its identification in 2005, many studies have investigated the anti-diabetic and anti-obesity effects of FGF21 and its analogues in animal models.
Study Design and Methodology
A study published in the International Journal of Obesity investigated the effects of FGF21 on obese, non-diabetic rhesus macaque monkeys. Ten monkeys (five males and five ovariectomized females) were maintained on a high-fat diet (HFD) for at least two years before the study. The animals were between 11 and 22 years of age, with body weights ranging from 8.3 to 21.1 kg. The high-fat diet contained a high content of fat and cholesterol, resembling the typical American diet.
The study involved a 12-week dose-escalating treatment with once-daily administration of native recombinant human FGF21. The initial dose was 10 μg/kg/day, followed by 30, 100, 300, and 1000 μg/kg/day. Nine of the ten animals were maintained on 1000 μg/kg/day for the last 6 weeks, while one female monkey, sensitive to the treatment, was maintained on 300 μg/kg/day.
Throughout the study, food intake was assessed daily, and body weight was measured weekly. Bone mineral content (BMC) and bone mineral density (BMD) were measured by DEXA scanning before the study and at several points during treatment and washout. Glucose tolerance was assessed using intravenous glucose tolerance tests (IVGTTs). Body composition was measured by MRI, and subcutaneous adipose tissue biopsies were collected. Various hormone concentrations, including leptin, adiponectin, IGF-1, CTX-1, osteocalcin, and myostatin, were also measured. Lipoprotein levels were analyzed by gel filtration chromatography.
Read also: Captive Marmoset Feeding
Key Findings
- Body Weight Reduction: FGF21 treatment resulted in an average body weight decrease of 17.6 ± 1.6% after 12 weeks. The weight loss was not due to reduced food intake, as no significant changes in food consumption were observed during the treatment period. During the washout period, food consumption increased compared to pre-dosing.
- Body Composition Changes: The body weight reduction was primarily due to a loss of fat mass, which decreased by 27.3 ± 4.2%. Concurrently, non-fat body mass decreased by 7.8 ± 2.1%. MRI scans showed the greatest fat loss in the intra-abdominal area, reduced by 38.5 ± 7.9%. Subcutaneous abdominal fat and retroperitoneal fat areas were also significantly reduced.
- Bone Health: BMC and BMD were not altered during the 12 weeks of treatment or during the washout period. However, CTX-1, a marker of bone resorption, increased after 8 and 12 weeks of treatment, suggesting potential effects on bone turnover.
- Glucose Metabolism: Overall glucose tolerance improved, with a small but significant decrease in HbA1C. Fasting insulin and c-peptide levels decreased significantly after 6 weeks of treatment. The insulin/c-peptide ratio was also significantly reduced, indicating better hepatic insulin clearance.
- Hormonal Changes: FGF21 treatment significantly decreased IGF-1 and increased IGFBP2. Total adiponectin and high molecular weight (HMW) adiponectin increased with treatment. The plasma level of myostatin, an inhibitor of skeletal muscle growth, decreased significantly upon treatment.
- Lipoprotein Levels: FGF21 reduced concentrations of plasma triglycerides and very low-density lipoprotein cholesterol.
Implications of the Study
The study's findings suggest that FGF21 can effectively reduce body weight in obese rhesus macaque monkeys without reducing food intake. The beneficial effects on body composition, insulin sensitivity, and plasma triglycerides further support the potential of FGF21 as a therapeutic agent for obesity and related metabolic disorders.
However, the observed increase in CTX-1 raises concerns about potential adverse effects on bone health, which warrants further investigation. Additionally, the study acknowledges that adverse effects, such as hepatic growth hormone resistance, low circulating IGF-1 levels, impaired linear growth, inhibition of female reproduction, and increased HPA axis activity, have been observed in mice chronically exposed to FGF21.
"Uncle Fat": A Case Study of Obesity in a Wild Macaque
The Story of "Uncle Fat"
In a stark contrast to the controlled environment of the FGF21 study, the story of "Uncle Fat" illustrates the consequences of human-animal interactions and the impact of unhealthy diets on wild primates. "Uncle Fat," a macaque monkey living near a floating market in Bangkok, Thailand, gained notoriety for his extreme obesity. Tourists regularly fed him junk food and sugary drinks, leading to a weight of 60 pounds, three times the average weight for his species.
Health Complications and Rescue
"Uncle Fat's" excessive weight led to serious health issues, including a high risk of heart disease and diabetes. Local wildlife officials captured him and placed him under the care of a veterinarian, Supakarn Kaewchot. Supakarn noted that the excess fat had formed a mass resembling a benign tumor.
Weight Loss Program
To address his critical condition, "Uncle Fat" was placed on a strict diet consisting of lean protein, fruits, and vegetables, limited to 400 grams twice a day. The goal was to reduce his weight to a healthy range and mitigate the risk of developing severe health complications.
Read also: Sweet and Savory Keto Treat
Lessons Learned
"Uncle Fat's" story highlights the dangers of feeding wild animals human food. While tourists may intend to be kind, providing unhealthy snacks and sugary drinks can have devastating consequences for the animals' health and well-being. This case underscores the importance of educating the public about responsible wildlife interactions and the need to protect animals from the harmful effects of human behavior.
Comparing FGF21 Treatment and Traditional Dieting
Contrasting Approaches
The FGF21 study and the "Uncle Fat" case study represent two distinct approaches to managing obesity in primates. The FGF21 study investigates a pharmaceutical intervention to promote weight loss and improve metabolic health. In contrast, "Uncle Fat's" case involves a traditional dietary intervention, restricting calorie intake and providing a balanced, healthy diet.
Efficacy and Feasibility
FGF21 treatment has shown promising results in reducing body weight and improving metabolic parameters in obese rhesus macaques. However, potential adverse effects on bone health and other physiological processes need to be carefully considered. Pharmaceutical interventions may be more suitable for controlled research settings or clinical applications where close monitoring is possible.
Traditional dieting, as implemented in "Uncle Fat's" case, can be effective in promoting weight loss and improving health outcomes. However, it requires strict adherence to the dietary plan and may be challenging to implement in wild or semi-wild animal populations. Educating the public about responsible feeding practices is crucial in preventing obesity in wild animals and ensuring their long-term well-being.
Complementary Strategies
In some cases, a combination of pharmaceutical and dietary interventions may be the most effective approach to managing obesity in primates. For example, FGF21 treatment could be used to initiate weight loss and improve metabolic health, while dietary modifications and lifestyle changes could help maintain weight loss and prevent relapse.
Read also: Omnivorous Capuchin Monkeys