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. 2022 Dec 5;14(23):5173.
doi: 10.3390/nu14235173.

Anti-Obesity Effects of Multi-Strain Probiotics in Mice with High-Carbohydrate Diet-Induced Obesity and the Underlying Molecular Mechanisms

Hye Rim Kim  1 , Eunsol Seo  1 , Seyeon Oh  2 , MinYeong Seo  3 , Kyunghee Byun  2   4 , Byung-Yong Kim  1
Affiliations

Anti-Obesity Effects of Multi-Strain Probiotics in Mice with High-Carbohydrate Diet-Induced Obesity and the Underlying Molecular Mechanisms

Hye Rim Kim et al. Nutrients. .

Abstract

Overconsumption of highly refined carbohydrates contributes significantly to the current obesity pandemics. Probiotic administration protects against weight gain in animals fed a high-fat diet (HFD). Nonetheless, the anti-obesity effects of probiotics in a high-carbohydrate diet (HCD)-induced obesity models are not well elucidated. Herein, C57BL/6N male mice were fed an HCD (70% kcal carbohydrate) for 12 weeks and were orally treated with multi-strain probiotics (MSPs) at 1010 CFU or saline every day for 6 weeks. MSPs contained Lactobacillus acidophilus DSM 24936, Lactiplantibacillus plantarum DSM 24937, and Limosilactobacillus reuteri DSM 25175. MSPs treatment not only ameliorated weight gain but also modulated the body fat composition altered by HCD. The MSPs also attenuated the expression of adipogenesis- and lipogenesis-related genes in HCD-fed mice. In addition, MSPs promoted the expression of lipolysis- and fatty acid oxidation-promoting factors in HCD-fed mice. Furthermore, MSPs modulated the expression of thermogenesis-related genes and the serum levels of obesity-related hormones altered by HCD. Treatment with MSPs positively reversed the Firmicutes/Bacteroidetes ratio, which is associated with a risk of obesity. Hence, this study explores the multifaceted anti-obesity mechanisms of MSPs and highlights their potential to be used as effective weight-management products.

Keywords: Firmicutes/Bacteroidetes ratio; high-carbohydrate diet; obesity; probiotics.

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Conflict of interest statement

CH Labs Corp. is a subsidiary company of CKD Healthcare (Seoul, Republic of Korea).

Figures

Figure 1
Figure 1
Inhibitory effect of multi-strain probiotics (MSPs) on lipid accumulation in vitro. (A) Relative inhibition of lipase activity (%). (B) Relative level of lipid content in 3T3-L1 cells. (C) Representative images of Oil Red O staining of 3T3-L1 cells in different groups (scale bar = 100 µm). Data are expressed as mean ± standard deviation. * p < 0.05; ** p < 0.01 vs. negative control. NO, undifferentiated 3T3-L1 cells; NC, negative control; PC, orlistat-treated; Probiotics, MSPs-treated.
Figure 2
Figure 2
Effect of MSPs on obesity in HCD-fed mice. (A) Mouse body weight over the course of 18 weeks. (B) Effect of MSPs on body weight after 6 weeks of administration. (C) Effect of MSPs on body fat percentage after 6 weeks of administration. Data are expressed as mean ± standard deviation (n = 5 per group). *** p < 0.001 vs. ND; ### p < 0.001 vs. HCD + placebo. Legend: HCD, high-carbohydrate diet; MSPs, multi-strain probiotics; ND, normal diet.
Figure 2
Figure 2
Effect of MSPs on obesity in HCD-fed mice. (A) Mouse body weight over the course of 18 weeks. (B) Effect of MSPs on body weight after 6 weeks of administration. (C) Effect of MSPs on body fat percentage after 6 weeks of administration. Data are expressed as mean ± standard deviation (n = 5 per group). *** p < 0.001 vs. ND; ### p < 0.001 vs. HCD + placebo. Legend: HCD, high-carbohydrate diet; MSPs, multi-strain probiotics; ND, normal diet.
Figure 3
Figure 3
Effect of MSPs on adipogenesis and lipogenesis in the visceral adipose tissues of HCD-fed mice. (A) PCNA DAB staining of representative histological sections of visceral adipose tissues. Scale bar = 50 µm. (B) Number of PCNA-positive cells in visceral adipose tissues. (C–E) mRNA expression of adipogenesis-related genes in visceral adipose tissues. (F–H) mRNA expression of lipogenesis-related genes in visceral adipose tissues. Data are expressed as mean ± standard deviation (n = 5 per group). *** p < 0.001 vs. ND; ### p < 0.001 vs. HCD + placebo. Legend: ACC, acetyl-CoA carboxylase; ACL, ATP citrate lyase; C/EBP, CCAAT/enhancer binding proteins; FAS, fatty acids synthase; HCD, high-carbohydrate diet; mRNA, messenger ribonucleic acid; MSPs, multi-strain probiotics; ND, normal diet; PCNA, antibodies to the proliferating cell nuclear antigen; PPARγ, peroxisome proliferator-activated receptor gamma; SREBP-1c, sterol regulatory element-binding protein-1c.
Figure 3
Figure 3
Effect of MSPs on adipogenesis and lipogenesis in the visceral adipose tissues of HCD-fed mice. (A) PCNA DAB staining of representative histological sections of visceral adipose tissues. Scale bar = 50 µm. (B) Number of PCNA-positive cells in visceral adipose tissues. (C–E) mRNA expression of adipogenesis-related genes in visceral adipose tissues. (F–H) mRNA expression of lipogenesis-related genes in visceral adipose tissues. Data are expressed as mean ± standard deviation (n = 5 per group). *** p < 0.001 vs. ND; ### p < 0.001 vs. HCD + placebo. Legend: ACC, acetyl-CoA carboxylase; ACL, ATP citrate lyase; C/EBP, CCAAT/enhancer binding proteins; FAS, fatty acids synthase; HCD, high-carbohydrate diet; mRNA, messenger ribonucleic acid; MSPs, multi-strain probiotics; ND, normal diet; PCNA, antibodies to the proliferating cell nuclear antigen; PPARγ, peroxisome proliferator-activated receptor gamma; SREBP-1c, sterol regulatory element-binding protein-1c.
Figure 4
Figure 4
Effect of MSPs on adipolysis and fatty acid oxidation in the visceral adipose tissues of HCD-fed mice. (A–C) mRNA expression of lipolysis-promoting genes in visceral adipose tissues. (D,E) mRNA expression of fatty acid oxidation-promoting genes in visceral adipose tissues. Data are expressed as mean ± standard deviation (n = 5 per group). *** p < 0.001 vs. ND; ### p < 0.001 vs. HCD + placebo. Legend: AC, adenylyl cyclase; ACO, acyl CoA oxidase; CPT-1A, carnitine palmitoyltransferase-1A; HCD, high-carbohydrate diet; HSL, hormone-sensitive lipase; mRNA, messenger ribonucleic acid; MSPs, multi-strain probiotics; ND, normal diet; PPAR-α, peroxisome proliferator-activated receptor alpha.
Figure 5
Figure 5
Effect of MSPs on thermogenesis in the visceral adipose tissues of HCD-fed mice. (A,B) mRNA expression of thermogenesis-related genes in visceral adipose tissues. (C) Core temperature of mice. Data are expressed as mean ± standard deviation (n = 5 per group). *** p < 0.001 vs. ND; # p < 0.05 vs. HCD + placebo; ### p < 0.001 vs. HCD + placebo. Legend: HCD, high-carbohydrate diet; mRNA, messenger ribonucleic acid; MSPs, multi-strain probiotics; ND, normal diet; PGC-1α, peroxisome proliferator-activated receptor-γ coactivator; UCP-1, uncoupling protein 1.
Figure 6
Figure 6
Effect of MSPs on serum adipokine levels in HCD-fed mice. (A) Serum leptin level. (B) Serum adiponectin level. (C) Serum insulin level. Data are expressed as mean ± standard deviation (n = 5 per group). *** p < 0.001 vs. ND; ### p < 0.001 vs. HCD + placebo. Legend: HCD, high-carbohydrate diet; ND, normal diet.
Figure 7
Figure 7
Effects of MSPs on the gut microbiota. (A) Bar chart of relative abundances of bacteria at the phylum level. (B) The Firmicutes/Bacteroidetes ratio of intestinal microbiome in mice. (C) Relative abundance of Lactobacilliaceae family members. (D) Relative abundance of the Roseburia genus. Data are expressed as mean ± standard deviation (n = 6–7 per group). ** p < 0.01 vs. ND, # p < 0.05 vs. HCD + placebo. Legend: HCD, high-carbohydrate diet; ND, normal diet.
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References

    1. Nam G.E., Kim Y.-H., Han K., Jung J.-H., Rhee E.-J., Lee S.-S., Kim D.J., Lee K.-W., Lee W.-Y., on behalf of the Taskforce Team of the Obesity Fact Sheet of the Korean Society for the Study of Obesity Obesity Fact Sheet in Korea, 2019: Prevalence of Obesity and Abdominal Obesity from 2009 to 2018 and Social Factors. J. Obes. Metab. Syndr. 2020;29:124–132. doi: 10.7570/jomes20058. - DOI - PMC - PubMed
    1. Kobyliak N., Conte C., Cammarota G., Haley A.P., Styriak I., Gaspar L., Fusek J., Rodrigo L., Kruzliak P. Probiotics in prevention and treatment of obesity: A critical view. Nutr. Metab. 2016;13:14. doi: 10.1186/s12986-016-0067-0. - DOI - PMC - PubMed
    1. Berticat C., Durand V., Raymond M. Refined Carbohydrate Consumption and Facial Attractiveness. Evol. Psychol. 2020;18:1474704920960440. doi: 10.1177/1474704920960440. - DOI - PMC - PubMed
    1. Bhardwaj B., O’Keefe E.L., O’Keefe J.H. Death by Carbs: Added Sugars and Refined Carbohydrates Cause Diabetes and Cardiovascular Disease in Asian Indians. Mo. Med. 2016;113:395–400. - PMC - PubMed
    1. Ludwig D.S., Ebbeling C.B., Rimm E.B. Carbohydrates, Insulin Secretion, and “Precision Nutrition”. Diabetes Care. 2022;45:1303–1305. doi: 10.2337/dci22-0009. - DOI - PubMed