A Multi-Ingredient Supplement Protects against Obesity and Infertility in Western Diet-Fed Mice

The Western diet (WD) predisposes to bodyweight gain and obesity and is linked to mitochondrial dysfunction, oxidative damage, inflammation, and multisystem disease, even affecting the reproductive organs, fertility, and pregnancy outcomes. In this study, we investigated the effects of multi-ingredi...

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Main Authors: Mats I. Nilsson, Linda May, Liza J. Roik, Matthew R. Fuda, Ashely Luo, Bart P. Hettinga, Adam L. Bujak, Mark A. Tarnopolsky
Format: Article
Language:English
Published: MDPI AG 2023-01-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/15/3/611
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author Mats I. Nilsson
Linda May
Liza J. Roik
Matthew R. Fuda
Ashely Luo
Bart P. Hettinga
Adam L. Bujak
Mark A. Tarnopolsky
author_facet Mats I. Nilsson
Linda May
Liza J. Roik
Matthew R. Fuda
Ashely Luo
Bart P. Hettinga
Adam L. Bujak
Mark A. Tarnopolsky
author_sort Mats I. Nilsson
collection DOAJ
description The Western diet (WD) predisposes to bodyweight gain and obesity and is linked to mitochondrial dysfunction, oxidative damage, inflammation, and multisystem disease, even affecting the reproductive organs, fertility, and pregnancy outcomes. In this study, we investigated the effects of multi-ingredient supplementation (MIS) with antioxidants, phytonutrients, and vitamins (‘Fertility Enhancer’; FE) on white adipose tissue (WAT) expansion, nonalcoholic fatty liver disease (NAFLD), and infertility in WD-fed C57BL/6J mice. Five-month-old male (M) and female (F) mice were fed a low-fat diet (LF) or a high fat/sucrose WD (HF) for six weeks, followed by six weeks of LF (3.64 kcal/g), HF (4.56 kcal/g), or HF combined with FE (4.50 kcal/g). A sub-set of animals were sacrificed at 12 weeks, while the remainder were harem-mated in a 1:2 male-to-female ratio, and singly housed during the gestational period. Two-way, factorial ANOVA analysis revealed a main effect of diet on bodyweight (BW), total body fat, % body fat, white adipose tissue mass, and liver lipid content (all <i>p</i> < 0.001), driven by the anti-obesogenic effects of the ‘Fertility Enhancer’. Similarly, a main effect of diet was found on PGC1-α mRNA levels (<i>p</i> < 0.05) and mitochondrial protein content (<i>p</i> < 0.001) in perigonadal WAT, with PGC1-α induction and higher complex II and complex III expression in FE vs. HF animals. Copulatory plug counts were higher in FE vs. HE couples (30% vs. 6%), resulting in more litters (4 vs. 0) and higher copulatory success (67% vs. 0%). Although the trends of all histology outcomes were suggestive of a benefit from the FE diet, only the number of atretic follicles and testicular mass were significant. Ovarian IL-1β mRNA induction was significantly attenuated in the FE group (<i>p</i> < 0.05 vs. HF) with CASP1 attenuation trending lower (<i>p</i> = 0.09 vs. HF), which is indicative of anti-inflammatory benefits of the ‘Fertility Enhancer.’ We conclude that supplementation with specific phytonutrients, antioxidants, and vitamins may have utility as an adjunctive therapy for weight management, fatty liver disease, and infertility in overweight and obese couples.
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spelling doaj.art-30a2aacde84a4dcdb427b5a4bdbb40aa2023-11-16T17:39:23ZengMDPI AGNutrients2072-66432023-01-0115361110.3390/nu15030611A Multi-Ingredient Supplement Protects against Obesity and Infertility in Western Diet-Fed MiceMats I. Nilsson0Linda May1Liza J. Roik2Matthew R. Fuda3Ashely Luo4Bart P. Hettinga5Adam L. Bujak6Mark A. Tarnopolsky7Department of Pediatrics, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, CanadaDepartment of Pediatrics, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, CanadaDepartment of Pediatrics, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, CanadaDepartment of Pediatrics, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, CanadaExerkine Corporation, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, CanadaExerkine Corporation, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, CanadaExerkine Corporation, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, CanadaDepartment of Pediatrics, McMaster University Medical Center (MUMC), Hamilton, ON L8N 3Z5, CanadaThe Western diet (WD) predisposes to bodyweight gain and obesity and is linked to mitochondrial dysfunction, oxidative damage, inflammation, and multisystem disease, even affecting the reproductive organs, fertility, and pregnancy outcomes. In this study, we investigated the effects of multi-ingredient supplementation (MIS) with antioxidants, phytonutrients, and vitamins (‘Fertility Enhancer’; FE) on white adipose tissue (WAT) expansion, nonalcoholic fatty liver disease (NAFLD), and infertility in WD-fed C57BL/6J mice. Five-month-old male (M) and female (F) mice were fed a low-fat diet (LF) or a high fat/sucrose WD (HF) for six weeks, followed by six weeks of LF (3.64 kcal/g), HF (4.56 kcal/g), or HF combined with FE (4.50 kcal/g). A sub-set of animals were sacrificed at 12 weeks, while the remainder were harem-mated in a 1:2 male-to-female ratio, and singly housed during the gestational period. Two-way, factorial ANOVA analysis revealed a main effect of diet on bodyweight (BW), total body fat, % body fat, white adipose tissue mass, and liver lipid content (all <i>p</i> < 0.001), driven by the anti-obesogenic effects of the ‘Fertility Enhancer’. Similarly, a main effect of diet was found on PGC1-α mRNA levels (<i>p</i> < 0.05) and mitochondrial protein content (<i>p</i> < 0.001) in perigonadal WAT, with PGC1-α induction and higher complex II and complex III expression in FE vs. HF animals. Copulatory plug counts were higher in FE vs. HE couples (30% vs. 6%), resulting in more litters (4 vs. 0) and higher copulatory success (67% vs. 0%). Although the trends of all histology outcomes were suggestive of a benefit from the FE diet, only the number of atretic follicles and testicular mass were significant. Ovarian IL-1β mRNA induction was significantly attenuated in the FE group (<i>p</i> < 0.05 vs. HF) with CASP1 attenuation trending lower (<i>p</i> = 0.09 vs. HF), which is indicative of anti-inflammatory benefits of the ‘Fertility Enhancer.’ We conclude that supplementation with specific phytonutrients, antioxidants, and vitamins may have utility as an adjunctive therapy for weight management, fatty liver disease, and infertility in overweight and obese couples.https://www.mdpi.com/2072-6643/15/3/611obesityinfertilitysubfertilityfatliverNAFLD
spellingShingle Mats I. Nilsson
Linda May
Liza J. Roik
Matthew R. Fuda
Ashely Luo
Bart P. Hettinga
Adam L. Bujak
Mark A. Tarnopolsky
A Multi-Ingredient Supplement Protects against Obesity and Infertility in Western Diet-Fed Mice
Nutrients
obesity
infertility
subfertility
fat
liver
NAFLD
title A Multi-Ingredient Supplement Protects against Obesity and Infertility in Western Diet-Fed Mice
title_full A Multi-Ingredient Supplement Protects against Obesity and Infertility in Western Diet-Fed Mice
title_fullStr A Multi-Ingredient Supplement Protects against Obesity and Infertility in Western Diet-Fed Mice
title_full_unstemmed A Multi-Ingredient Supplement Protects against Obesity and Infertility in Western Diet-Fed Mice
title_short A Multi-Ingredient Supplement Protects against Obesity and Infertility in Western Diet-Fed Mice
title_sort multi ingredient supplement protects against obesity and infertility in western diet fed mice
topic obesity
infertility
subfertility
fat
liver
NAFLD
url https://www.mdpi.com/2072-6643/15/3/611
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