Relationship Between Dietary Nutrient Intake and Autophagy—Related Genes in Obese Humans: A Narrative Review
Abstract
:1. Introduction
2. Methods
3. The Regulatory Mechanism of Autophagy
4. Autophagy and Obesity Links
4.1. Insulin as a Potent Inhibitor of Autophagy
4.2. Role of Autophagy in Fatty Liver Modulation
5. Autophagy Related Genes in Obese Humans as a Therapeutic Target
Therapeutic Modulation of Autophagy in Obese Humans
- (a)
- Metformin—multiple signaling pathways mediate the effect of metformin, which is related to the improvement in the induction of hepatic autophagy and the inhibition of the induction of adipose tissue autophagy [87];
- (b)
- SGLT2 inhibitors—the effects of SGLT2 inhibitors promote the activation of AMPK, SIRT1, SIRT3, and SIRT6, and PGC-1α, decrease the activation of mTOR in diverse tissues under stress, and increase biomarkers of autophagy flux (LAMP-1, Beclin-1) [88];
- (c)
- DPP4 (Dipeptidyl-Peptidase 4) inhibitors promote the autophagy process to decrease triglycerides (TGs), low-density lipoproteins (LDLs) and high-density lipoproteins (HDLs), as well as nitro-oxidative stress, via a mechanism dependent on autophagy modulation [89];
- (d)
- GLP-1 receptor agonists (GLP-1 RA) play a crucial role in regulating autophagic flux, as GLP-1R knockdown suppresses the autophagy induction and mTOR inhibition induced by GLP-1 peptide treatment. Additionally, GLP-1R expression was found to be decreased in certain conditions, such as high-fat diet-induced liver steatosis [90];
- (e)
- GLP/GIP receptor agonist—this novel antidiabetic, anti-obesity drug displayed a protective cardiac effect, preventing cell death, fibrosis and hypertrophy with a potential positive impact on cardiac remodeling. It also plays a crucial role in the autophagic process via the AMPK/mTOR pathway [91].
6. Obesity Inhibits or Activates Autophagy?
7. Nutritional Interventions for Autophagy Modulations in Overweight/Obese Humans
7.1. Calorie Restriction; Intermittent Fasting
7.2. Mediterranean Diet (Met Diet)
7.3. Dietary Polyphenols
7.4. Dietary Fatty Acids
7.5. Diet Modifications
7.6. Protein Intake
Dietary Strategies | Model of Obesity | Parameter Studies | Effect on Autophagy | References |
---|---|---|---|---|
Calorie restriction or Intermittent fasting | Skeletal muscle of body fat-matched endurance athletes; skeletal muscle of obese women; obese humans (subcutaneous, white adipose tissue) | Decreased mTOR signaling through reducing insulin and IGF-1 levels and increased the AMP/ATP ratio, which leads to the activation of AMPK as well as several other products involved in the stimulation of this process (ATG 5, ATG6, ATG7, ATG8, LC3-II, Beclin1, p62, SIRT1, LAMP2, ULK1 and ATG101) | Enhanced | [96,97,98,99,100,101,102,103,104] |
Calorie restriction 25% for 7 weeks | Peripheral blood mononuclear cells (PBMNCs) of overweight male | Activated AMPK and SIRT1 | Enhanced | [105] |
Mediterranean diet (MD) vs. Mediterranean diet with almonds (MDSA) | Obese humans (subcutaneous, white adipose tissue) | Elevated levels of autophagy-related proteins ATG7 and ATG12 were observed in the VAT of the MDSA and ATG5 showed a non-significant trend | Enhanced | [125] |
Epigallocatechin-3-gallate + resveratrol (280 mg + 80 mg/d) vs. placebo—12 weeks | Obese humans (subcutaneous, white adipose tissue) | Activated gene expressions of ATP6V1A, ATP6V1H, CD68, HSL/LIPE, LAMP2, PI4K2A, UCP2, GAPDH | Enhanced | [128] |
Resveratrol 150 mg once daily for 30 days | Obese men (skeletal muscle) | Activated AMPK, increased SIRT1 and PGC-1α protein levels | Enhanced | [132] |
Resveratrol 150 mg once daily for 30 days | Obese men (skeletal muscle) | Activated TFEB (transcriptional factor EB) expression; inhibited mTOR activity | Enhanced | [133] |
Resveratrol (500 mg/d) vs. Calorie restriction (1000 kcal/d) | Overweight humans (blood) | Resveratrol and caloric restriction significantly increased serum concentrations of SIRT1 proteins | Enhanced | [136] |
4 diets followed a period of 12 weeks: a diet high in saturated fatty acids (HSFA), a diet rich in monounsaturated fatty acids (HMUFA), and two low-fat, high-complex-carbohydrate diets, one of which was supplemented with long-chain n-3 polyunsaturated fatty acids (LFHCC n-3) while the other received a placebo (LFHCC) | Obese humans (subcutaneous); white adipose tissue | HMUFA diet significantly increased expression of BECN1 and ATG7. LFHCC and LFHCC n-3 diets led to an increase in the expression of the apoptosis-related gene CASP3. Additionally, the LFHCC n-3 diet showed a tendency to increase the expressions of other autophagy markers, such as LC3, LAMP2, and ULK1. | Enhanced | [145] |
Low-fat, high-carbohydrate diet (LF) vs. moderate-fat, low-carbohydrate diet (MF) for 10 weeks | Obese humans (subcutaneous); white adipose tissue | Expressions of FABP4, SIRT3, NR3C1, GABARAPL2, and FNTA genes were 15–65% higher in the MF than the LF | Enhanced in MF diet vs. LF | [146,147] |
Hypocaloric diet (1500–1600 kcal/day) and low protein LP (10%) vs. hypocaloric (1500–1600 kcal/day) and high protein (30E%) for 3 weeks prior to bariatric surgery | Liver sample collected during surgery | Significantly elevated autophagy flux and FGF21 levels in the livers of patients in the LP diet versus HP | Enhanced in LP diet vs. HP | [148] |
8. Limitations
9. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Bednarczyk, M.; Dąbrowska-Szeja, N.; Łętowski, D.; Dzięgielewska-Gęsiak, S.; Waniczek, D.; Muc-Wierzgoń, M. Relationship Between Dietary Nutrient Intake and Autophagy—Related Genes in Obese Humans: A Narrative Review. Nutrients 2024, 16, 4003. https://doi.org/10.3390/nu16234003
Bednarczyk M, Dąbrowska-Szeja N, Łętowski D, Dzięgielewska-Gęsiak S, Waniczek D, Muc-Wierzgoń M. Relationship Between Dietary Nutrient Intake and Autophagy—Related Genes in Obese Humans: A Narrative Review. Nutrients. 2024; 16(23):4003. https://doi.org/10.3390/nu16234003
Chicago/Turabian StyleBednarczyk, Martyna, Nicola Dąbrowska-Szeja, Dariusz Łętowski, Sylwia Dzięgielewska-Gęsiak, Dariusz Waniczek, and Małgorzata Muc-Wierzgoń. 2024. "Relationship Between Dietary Nutrient Intake and Autophagy—Related Genes in Obese Humans: A Narrative Review" Nutrients 16, no. 23: 4003. https://doi.org/10.3390/nu16234003
APA StyleBednarczyk, M., Dąbrowska-Szeja, N., Łętowski, D., Dzięgielewska-Gęsiak, S., Waniczek, D., & Muc-Wierzgoń, M. (2024). Relationship Between Dietary Nutrient Intake and Autophagy—Related Genes in Obese Humans: A Narrative Review. Nutrients, 16(23), 4003. https://doi.org/10.3390/nu16234003