Impact of body weight gain on hepatic metabolism and hepatic inflammatory cytokines in comparison of Shetland pony geldings and Warmblood horse geldings

Background Non-alcoholic fatty liver disease is known as determining part of human obesity. The impact of body weight (BW) gain on liver metabolism has not been extensively investigated yet. Objectives To investigate hepatic alterations caused by increasing BW in ponies and horses. Animals A total of 19 non-obese equines (10 Shetland ponies, geldings; nine Warmblood horses, geldings). Methods Animals received 200% of their metabolizable maintenance energy requirements for 2 years. Serum alkaline phosphatase, glutamate dehydrogenase (GLDH), aspartate aminotransferase (AST), and gamma-glutamyl transferase activities and bile acids were analyzed several times during 2 years of hypercaloric diet. Hepatic lipid content and hepatic levels of the interleukin (IL)-6, tumor necrosis factor α (TNFα), cluster of differentiation (CD) 68, IL-1β, lipoprotein lipase (LPL), fatty acid-binding protein 1, chemerin and nuclear factor-κB mRNAs were assessed at the start of the study and after 1 and 2 years of excess energy intake. Results The mean (±SD) BW gain recorded during 2 years of excess energy intake was 29.9 ± 19.4% for ponies and 17 ± 6.74% for horses. The hepatic lipid content was not profoundly affected by increasing BW. Levels of the IL-6, TNFα, CD68 and IL-1β mRNAs did not change during BW gain. Levels of the chemerin mRNA increased significantly in both breeds (ponies: P = 0.02; horses: P = 0.02) in response to BW gain. Significant differences in serum GLDH and AST activities, serum bile acid concentrations and hepatic levels of the LPL mRNA were observed between ponies and horses at the end of the study. Conclusions Chemerin might represent an interesting marker for future equine obesity research. Interestingly, steatosis caused by increasing BW may occur later in the development of obesity in equines than in humans. Additionally, the hepatic metabolism exhibits differences between ponies and horses, which may explain in part the greater susceptibility of ponies to obesity-associated metabolic dysregulations.

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Effects of maternal diet-induced obesity on metabolic disorders and age-associated miRNA expression in the liver of male mouse offspring

International Journal of Obesity ◽

10.1038/s41366-021-00985-1 ◽

2021 ◽

Author(s):

Laís Vales Mennitti ◽

Asha A. M. Carpenter ◽

Elena Loche ◽

Lucas C. Pantaleão ◽

Denise S. Fernandez-Twinn ◽

...

Keyword(s):

Body Weight ◽

Lipid Content ◽

Metabolic Disorders ◽

Maternal Obesity ◽

Maternal Diet ◽

Whole Body ◽

Mrna Levels ◽

Hepatic Lipid ◽

Diet Induced Obesity ◽

Hepatic Lipid Content

Abstract Objective This study investigated the effect of maternal obesity on aged-male offspring liver phenotype and hepatic expression of a programmed miRNA. Methods A mouse model (C57BL/6 J) of maternal diet-induced obesity was used to investigate fasting-serum metabolites, hepatic lipid content, steatosis, and relative mRNA levels (RT-PCR) and protein expression (Western blotting) of key components involved in hepatic and mitochondrial metabolism in 12-month-old offspring. We also measured hepatic lipid peroxidation, mitochondrial content, fibrosis stage, and apoptosis in the offspring. To investigate potential mechanisms leading to the observed phenotype, we also measured the expression of miR-582 (a miRNA previously implicated in liver cirrhosis) in 8-week-old and 12-month-old offspring. Results Body weight and composition was similar between 8-week-old offspring, however, 12-month-old offspring from obese mothers had increased body weight and fat mass (19.5 ± 0.8 g versus 10.4 ± 0.9 g, p < 0.001), as well as elevated serum levels of LDL and leptin and hepatic lipid content (21.4 ± 2.1 g versus 12.9 ± 1.8 g, p < 0.01). This was accompanied by steatosis, increased Bax/Bcl-2 ratio, and overexpression of p-SAPK/JNK, Tgfβ1, Map3k14, and Col1a1 in the liver. Decreased levels of Bcl-2, p-AMPKα, total AMPKα and mitochondrial complexes were also observed. Maternal obesity was associated with increased hepatic miR-582-3p (p < 0.001) and miR-582-5p (p < 0.05). Age was also associated with an increase in both miR-582-3p and miR-582-5p, however, this was more pronounced in the offspring of obese dams, such that differences were greater in 12-month-old animals (−3p: 7.34 ± 1.35 versus 1.39 ± 0.50, p < 0.0001 and −5p: 4.66 ± 1.16 versus 1.63 ± 0.65, p < 0.05). Conclusion Our findings demonstrate that maternal diet-induced obesity has detrimental effects on offspring body composition as well as hepatic phenotype that may be indicative of accelerated-ageing phenotype. These whole-body and cellular phenotypes were associated with age-dependent changes in expression of miRNA-582 that might contribute mechanistically to the development of metabolic disorders in the older progeny.

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Comment on “Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women”

Science ◽

10.1126/science.abj1696 ◽

2021 ◽

Vol 373 (6554) ◽

pp. eabj1696

Author(s):

Charles Brenner

Keyword(s):

Placebo Group ◽

Insulin Sensitivity ◽

Randomized Trial ◽

Lipid Content ◽

Liver Fat ◽

Hepatic Lipid ◽

Nicotinamide Mononucleotide ◽

Hepatic Lipid Content

Yoshino et al. (Reports, 11 June 2021, p. 1224) have reported that nicotinamide mononucleotide (NMN) increases muscle insulin sensitivity in prediabetic women. However, the 13 women who received NMN had hepatic lipid content of 6.3 ± 1.2%, whereas the 12 in the placebo group had 14.8 ± 2.0% (P = 0.003). Given that a target of NMN is liver fat clearance, this was not an effectively randomized trial.

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Pycnogenol protects against diet-induced hepatic steatosis in apolipoprotein-E-deficient mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00009.2017 ◽

2018 ◽

Vol 315 (2) ◽

pp. E218-E228 ◽

Cited By ~ 2

Author(s):

Difei Wang ◽

Huiying Cong ◽

Xiaoli Wang ◽

Yanli Cao ◽

Shoichiro Ikuyama ◽

...

Keyword(s):

Lipid Metabolism ◽

Apolipoprotein E ◽

Hepatic Steatosis ◽

Inflammatory Cytokines ◽

Lipid Content ◽

Acid Uptake ◽

Short Term Treatment ◽

Hepatic Lipid ◽

Deficient Mice ◽

Hepatic Lipid Content

PycnogenolR (PYC), a combination of active flavonoids derived from French maritime pine bark, is a natural antioxidant that has various pharmacological activities. Here, we investigated the beneficial effect of PYC on diet-induced hepatic steatosis. Apolipoprotein E (ApoE)-deficient male mice were administered PYC at oral doses of 30 or 100 mg·kg−1·day−1 for 2 wk in advance and were then fed a high-cholesterol and -fat diet (HCD) for 8 wk. Biochemical, immunohistochemical, and gene expression analyses were conducted to explore the effect of PYC on lipid metabolism in ApoE-deficient mice on a HCD. Short-term treatment with HCD in ApoE-deficient mice induced hepatic injuries, such as lipid metabolism disorder and hepatic histopathological changes. We found that PYC reduced body weight and the increase of serum lipids that had been caused by HCD. Supplementation of PYC significantly reduced lipid deposition in the liver, as shown by the lowered hepatic lipid content and histopathological lesions. We subsequently detected genes related to lipid metabolism and inflammatory cytokines. The study showed that PYC markedly suppressed the expression of genes related to hepatic lipogenesis, fatty acid uptake, and lipid storage while increasing the lipolytic gene, which thus reduced hepatic lipid content. Furthermore, PYC mainly reduced the expression of inflammatory cytokines and the infiltration of inflammatory cells, which were resistant to the development of hepatic steatosis. These results demonstrate that PYC protects against the occurrence and development of hepatic steatosis and may provide a new prophylactic approach for nonalcoholic fatty liver disease (NAFLD).

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Hypoglycemic Effect of Vitexin in C57BL/6J Mice and HepG2 Models

Journal of Food Quality ◽

10.1155/2021/5535476 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Weidong Xu ◽

Jiayao Li ◽

Weipeng Qi ◽

Ye Peng

Keyword(s):

Insulin Resistance ◽

Body Weight ◽

Weight Gain ◽

Blood Glucose ◽

Glucose Uptake ◽

Lipid Content ◽

Hepg2 Cells ◽

Body Weight Gain ◽

Tnf Α ◽

Hepatic Lipid Content

Apigenin-8-C-glucoside (vitexin), a natural phytochemical contained in hawthorn, has been reported to have versatile beneficial bioactivities, such as antioxidation, anticancer property, and adipogenesis inhibition. The present research aimed to determine the influence of vitexin on insulin resistance elicited by HFD in mice and HepG2 cells. Vitexin markedly alleviated body weight gain and improved glucose and insulin intolerance induced by HFD. Vitexin partially normalized blood glucose, cholesterol, TNF-α, and hepatic lipid content. Moreover, vitexin recovered the reduced glucose uptake induced by glucosamine. The present results indicate that vitexin prevents HFD-induced insulin resistance.

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Diagnostic performance of cytology for assessment of hepatic lipid content in dairy cattle

Journal of Dairy Science ◽

10.3168/jds.2017-12897 ◽

2018 ◽

Vol 101 (2) ◽

pp. 1379-1387 ◽

Cited By ~ 4

Author(s):

M.M. Fry ◽

B. Yao ◽

C. Ríos ◽

C. Wong ◽

S. Mann ◽

...

Keyword(s):

Dairy Cattle ◽

Lipid Content ◽

Diagnostic Performance ◽

Hepatic Lipid ◽

Hepatic Lipid Content

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Role of patatin-like phospholipase domain-containing 3 gene for hepatic lipid content and insulin resistance in diabetes

10.2337/figshare.12315737.v1 ◽

2020 ◽

Author(s):

Oana P. Zaharia ◽

Klaus Strassburger ◽

Birgit Knebel ◽

Yuliya Kupriyanova ◽

Yanislava Karusheva ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Lipid Content ◽

Whole Body ◽

Hepatic Lipid ◽

Insulin Resistant ◽

Increased Risk ◽

Glucose Tolerant ◽

Hepatic Lipid Content

<a>Objective</a>: The rs738409(G) single-nucleotide polymorphism (SNP) in the patatin-like phospholipase domain-containing 3 (PNPLA3) gene associates with increased risk and progression of nonalcoholic fatty liver disease (NAFLD). As the recently-described severe insulin-resistant diabetes (SIRD) cluster specifically relates to NAFLD, this study examined whether this SNP differently associates with hepatic lipid content (HCL) and insulin sensitivity in recent-onset diabetes mellitus. Research Design and Methods: A total of 917 participants of the German Diabetes Study underwent genotyping, hyperinsulinemic-euglycemic clamps with stable isotopic tracer dilution and magnetic resonance spectroscopy. Results: The G allele associated positively with HCL (β=0.36, p<0.01), independent of age, sex and BMI across the whole cohort, but not in the individual clusters. SIRD exhibited lowest whole-body insulin sensitivity compared to severe insulin-deficient (SIDD), moderate obesity-related (MOD), moderate age-related (MARD) and severe autoimmune diabetes clusters (SAID; all p<0.001). Interestingly, SIRD presented with higher prevalence of the rs738409(G) SNP compared to other clusters and the glucose-tolerant control group (p<0.05). HCL was higher in SIRD [13.6 (5.8;19.1)%] compared to MOD [6.4 (2.1;12.4)%, p<0.05], MARD [3.0 (1.0;7.9)%, p<0.001], SAID [0.4 (0.0;1.5)%, p<0.001] and the glucose tolerant group [0.9 (0.4;4.9)%, p<0.001]. Although the PNPLA3 polymorphism did not directly associate with whole-body insulin sensitivity in SIRD, the G allele carriers had higher circulating free fatty acid concentrations and greater adipose-tissue insulin resistance compared to non-carriers (both p<0.001). Conclusions: Members of the severe insulin resistant diabetes cluster are more frequently carriers of the rs738409(G) variant. The SNP-associated adipose-tissue insulin resistance and excessive lipolysis may contribute to their NAFLD.

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