Dietary medium-chain fatty acids reduce food intake via the GDF15-GFRAL axis in mice

Kanta, Josephine M.; Deisen, Luisa; Johann, Kornelia; Holm, Stephanie; Lundsgaard, Annemarie; Lund, Jens; Jähnert, Markus; Schürmann, Annette; Clemmensen, Christoffer; Kiens, Bente; Fritzen, Andreas M.; Kleinert, Maximilian

doi:10.1016/j.molmet.2023.101760

Cited by 7 publications

(8 citation statements)

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“…The change was attenuated in GFRAL-deficient mice. No changes were seen in mice that were orally administered long-chain fatty acids [44], indicating that the production of medium-chain fatty acids in a HFD setting may be a factor that promotes the increase in GDF15 and suppresses food intake.…”

Section: The Relationship Between Gdf15 and Weight Changementioning

confidence: 95%

“…Neutralizing GDF15 with an antibody abolished this effect, suggesting that GDF15 can improve insulin sensitivity and reverse insulin resistance. GDF15 depletion does not cause significant changes in In NCD-fed mice [19,26,44] In HFD-fed mice [27,29,47,51] In HFD-fed mice [41,51,52] In NCD-fed mice [19,26,44] In HFD-fed mice [45][46][47][48] In obese cynomolgus monkeys [40,49] In HFD-fed mice [45][46][47] In obese mouse models [24,49] In obese mouse models [24,49] In obese cynomolgus monkeys [40,49] In obese cynomolgus monkeys [40,49] In shrews [50] In shrews [50] External factors (drugs/ surgery/exercise)…”

Section: Gdf15 Improves Insulin Resistancementioning

confidence: 99%

“…Eliminates the reduced food intake In NCD-fed mice [44,45] In NCD-fed mice [44,45] In HFD-fed mice [28,39,41,45,48] In HFD-fed mice [39,41,45,48] No effect on HFD-fed mice [38] No effect on HFDfed mice [38] ↑, increase; ↓, decrease; GDF15, growth differentiation factor-15; GFRAL, glial cell-derived neurotrophic factor family receptor alpha-like; HFD, high-fat diet; NCD, normal chow diet.…”

Section: Eliminates the Reduced Food Intakementioning

confidence: 99%

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Research Progress on the Role and Mechanism of GDF15 in Body Weight Regulation

Dong,

2023

Obes Facts

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Background: Growth differentiation factor-15 (GDF15) is a member of the growth differentiation factor subfamily in the transforming growth factor beta superfamily. GDF15 has multiple functions and can regulate biological processes. High levels of GDF15 in the circulation can affect metabolic processes. Studies have shown that GDF15 is associated with changes in body weight. Summary: This review reviews the current knowledge on the relationship between GDF15 and body weight change, focusing on the role and mechanism of GDF15 in body weight regulation. GDF15 plays an important role in reducing food intake, improving insulin resistance, and breaking down fat, suggesting that GDF15 has an important regulatory effect on body weight. The mechanism by which GDF15 causes reduced food intake may be related to changes in food preference, delayed gastric emptying, and conditioned taste aversion. GDF15 can combat insulin resistance induced by inflammation or protect β cell from apoptosis. GDF15 probably promotes lipolysis through a brain-somatic tissue circuit. Several factors and related signaling pathways are also mentioned that can contribute to the effects of GDF15 on reducing weight. Key Message: GDF15 plays an important role in weight regulation and provides a new direction for the treatment of obesity. Its effects on resisting obesity are of great significance to inhibiting the progression of metabolic diseases. It is expected to become a new target for regulating body weight, improving obesity, and treating metabolic diseases such as diabetes.

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Section: The Relationship Between Gdf15 and Weight Changementioning

confidence: 95%

Section: Gdf15 Improves Insulin Resistancementioning

confidence: 99%

Section: Eliminates the Reduced Food Intakementioning

confidence: 99%

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Research Progress on the Role and Mechanism of GDF15 in Body Weight Regulation

Dong,

2023

Obes Facts

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“…The medium-chain oils, which mainly consist of medium-chain triglycerides (MCTs), are known to have some health benefits in vivo. MCT treatment was shown to decrease food intake and BW gain, improve lipid metabolism, and induce thermogenic features both in the liver and the adipose tissue [17][18][19]. MCT intervention can also prevent postprandial hypertriglyceridemia in moderately hypertriglyceridemic patients [20] and ameliorate insulin resistance and hyperglycemia in vivo [21,22].…”

Section: Introductionmentioning

confidence: 99%

Effect of Different Medium-Chain Triglycerides on Glucose Metabolism in High-Fat-Diet Induced Obese Rats

Xia,

Wang,

et al. 2024

Foods

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Obesity can be associated with significant metabolic disorders. Our previous study found that medium-chain triglycerides (MCTs) improved lipid metabolism in obese rats. However, scant attention has been given to exploring the impact of MCTs on glucose metabolism in obese rats. This study is designed to examine the effects and mechanisms of three distinct MCTs on glucose metabolism in obese rats. To induce obesity, Sprague–Dawley (SD) rats were fed a high-fat diet, followed by a 12-week treatment with caprylic triglyceride (CYT), capric triglyceride (CT), and lauric triglyceride (LT). The results showed that three types of MCT intervention reduced the levels of lipids (TC, TG, LDL-c, and HDL-c), hyperglycemia, insulin resistance (insulin, OGTT, HOMA-IR, and ISI), and inflammatory markers (IL-4, IL-1β, and TNF-α) in obese rats (p < 0.01), The above parameters have been minimally improved in the high-fat restoring group (HR) group. MCTs can modulate the PI3K/AKT signaling pathways to alleviate insulin resistance and improve glucose metabolism in obese rats. Furthermore, MCTs can activate peroxisome proliferator-activated receptor (PPAR) γ and reduce the phosphorylation of PPARγser237 mediated by CDK5, which can improve insulin sensitivity without lipid deposition in obese rats. Among the MCT group, CT administration performed the best in the above pathways, with the lowest blood glucose level and insulin resistance. These findings contribute to a deeper understanding of the connection between health benefits and the specific type of MCT employed.

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“…SCFAs and MCFAs, defined as fatty acids with 2–6 and 8–12 carbon atoms in the acyl chain, respectively, have garnered significant attention for their potential benefits in inducing weight loss. 2,4,5,9 SCFAs, such as acetate, propionate, and butyrate, play a significant role in appetite regulation by influencing the release of appetite-regulating hormones, such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), leading to decreased food intake and increased feelings of satiety. 2 Recently, it was shown that SCFA supplementation can effectively combat obesity in adolescents.…”

Section: Introductionmentioning

confidence: 99%