The effects that fatty acids (FAs) exert on G protein-coupled receptor-120 (GPR120) levels, a receptor for FAs, are still unknown. We analyzed the association between GPR120 and obesity, and the FA effects on its expression.
Methods and results
GPR120 levels were analyzed in visceral adipose tissue (VAT) from nonobese and morbidly obese subject. VAT GPR120 mRNA and protein levels were lower in morbidly obese subjects (p = 0.004). After, these subjects underwent a high-fat meal. GPR120 mRNA expression in peripheral blood mononuclear cells in the fasting state was lower in morbidly obese subjects (p = 0.04), with a decrease 3 h after a high-fat meal only in morbidly obese subjects (p = 0.043). Also, incubations of visceral adipocytes from these subjects were made with different FAs. In nonobese subjects, palmitic, oleic, linoleic, and docosahexaenoic acids produced an increase in GPR120 mRNA and protein levels (p < 0.05). In morbidly obese subjects, only linoleic acid produced an increase in GPR120 mRNA and protein levels (p < 0.05).
Morbidly obese subjects had lower GPR120 mRNA and protein levels in VAT and a lower mRNA expression after a high-fat meal in peripheral blood mononuclear cells. The FAs effect on GPR120 mRNA and protein levels in visceral adipocytes was lower in morbidly obese subjects.
Alex’s Notes: Fatty acids (FAs) aren’t just little molecules floating in your blood. They also play a variety of roles in physiological processes of the body and act as signaling molecules, with difference FAs having difference effects. One of the receptors that they interact with is G protein-coupled receptor-120 (GPR120), which regulates numerous processes including gut hormone secretion, inflammation, and appetite. It also regulates fat cell development and growth, and obesity seems to be associated with increased GPR120 in both visceral and subcutaneous fat tissue. The study at hand aimed to further out understanding of this seemingly important receptor in obesity by investigating the association between obesity and expression of GPR120 in fat tissue, whether obesity may modify the effects of different FAs on GPR120 expression, and the acute changes in GPR120 expression in both lean and obese humans in response to a high-fat meal.
The subjects were either morbidly obese (BMI greater than 40) or normal weight (BMI below 25), but all were free from chronic diseases such as type-2 diabetes, cardiovascular disease, arthritis, or acute inflammation or infection, and none were taking medications. Contrary to the study cited above, GPR120 expression was lower in the visceral fat of the obese subjects than the nonobese subjects, and there was no difference in subcutaneous fat tissue expression. However, the nonobese subjects did show a significant difference between expression of their own visceral and subcutaneous fat, while there was no difference in the obese subjects. The visceral fat expression also had a significant inverse correlation with BMI. Regardless of the difference between these results and those of the previously mentioned study, we know that visceral fat plays a huge role in metabolic risk, suggesting that GPR120 is associated with obesity and its comorbidities. Moreover, mice without GPR120 develop obesity, increased inflammation, and insulin resistance, supporting its important role in health.
With that in mind, three hours after a high-fat meal consisting of 60 grams of fat (12g saturated, 35g monounsaturated, and 13g polyunsaturated omega-6), GPR120 expression increased significantly in nonobese subjects, but actually decreased in the obese subjects. Since underexpression of GPR120 seems to relate to obesity, this suggests that high-fat meals are not treated well by the obese subjects. Looking at the specific effects of the different FAs (palmitic, oleic, linoleic, DHA); all four produced a significant increase in GPR120 in nonobese subjects with linoleic acid being the most potent. In the obese subjects, only linoleic acid produced an increase in GPR120 expression. This suggests that the receptor is extra sensitive to the omega-6 FA, but unfortunately the doses of FAs used in this in-vitro experiment were well below what is experienced during the in-vivo postprandial period.
It is interesting to see how our genes interact with the environment. It appears that GPR120 is low in the obese and plays a large role in anti-inflammatory and insulin-sensitizing responses to food intake, as demonstrated by its significant increase in nonobese subjects upon eating. However, the typical high-fat Western meals commonly consumed by obese persons may actually be decreasing the expression of GPR120 in the obese and contributing to the development of other metabolic syndrome conditions.