Both prolonged high-fat diet consumption and calorie restriction boost hepatic NAD+ metabolism in mice

Wei, Xiaojing; Wei, Chen; Tan, Yutian; Xiao, Dong; Zhao, Yang; Yan, Jiaqi; Luo, Xiao

doi:10.1016/j.jnutbio.2023.109296

Cited by 6 publications

(3 citation statements)

References 62 publications

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“…Nnmt gene expression was suppressed in liver by MNAM at GD18.5 but increased in sWAT by MNAM at GD15.5. Our previous study showed that HFD consumption increases NNMT expression in sWAT but not in liver ( Wei et al 2020 , 2023 ). Our data further indicate the tissue-specific function of Nnmt.…”

Section: Discussionmentioning

confidence: 99%

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N1-methylnicotinamide impairs gestational glucose tolerance in mice

Wei,

Tan,

Huang

et al. 2023

Journal of Molecular Endocrinology

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N1-methylnicotinamide (MNAM), a product of methylation of nicotinamide through nicotinamide N-methyltransferase, displays anti-diabetic effects in male rodents. This study aimed to evaluate the ameliorative potential of MNAM on glucose metabolism in gestational diabetes mellitus (GDM) model. C57BL/6N mice were fed with high fat diet (HFD) for 6 weeks before pregnancy and throughout gestation to establish the GDM model. Pregnant mice were treated with 0.3% or 1% MNAM during gestation. MNAM supplementation in CHOW diet and HFD both impaired the glucose tolerance at gestational day 14.5 without changes in insulin tolerance. However, it reduced hepatic lipid accumulation as well as mass and inflammation in visceral adipose tissue. MNAM treatment decreased GLUT4 mRNA and protein expression in skeletal muscle, where NAD+ salvage synthesis and antioxidant defenses were dampened. NAD+/Sirtuin system was enhanced in liver, which subsequently boosted hepatic gluconeogenesis. GLUT1 protein was deminished in placenta by MNAM. In addition, weight of placenta, fetus weight or litter size were not affected by MNAM treatment. The decreased GLUT4 in skeletal muscle, boosted hepatic gluconeogenesis and dampened GLUT1 in placenta jointly contribute to the impairment of GTT by MNAM. Our data provide evidences for the careful usage of MNAM in treatment of GDM.

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Section: Discussionmentioning

confidence: 99%

“…H&E and Oil Red O staining in liver samples were prepared as described previously ( Wei et al 2023 ). Placentae were fixed in 4% PFA, embedded in paraffin, and sectioned in the vertical plane at 3 μm thickness.…”

Section: Methodsmentioning

confidence: 99%

N1-methylnicotinamide impairs gestational glucose tolerance in mice

Wei,

Tan,

Huang

et al. 2023

Journal of Molecular Endocrinology

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“…Adipose FA mobilization is the result of the cleavage of triglycerides by Adipose triglyceride lipase (ATGL) and diglycerides by hormone sensitive lipase (HSL) [ 10 ], which is particularly impacted by fasting [ 11 ]. Despite decreased hepatic lipogenesis during prolonged fasting and caloric restriction [ 12 , 13 ], lipids accumulate in the liver. This has been shown to be the result of competition between mitochondrial and peroxisomal beta oxidation [ 14 ], and the increased supply of non-esterified fatty acids released from white adipose tissue [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Exercise Equals the Mobilization of Visceral versus Subcutaneous Adipose Fatty Acid Molecules in Fasted Rats Associated with the Modulation of the AMPK/ATGL/HSL Axis

et al. 2023

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Combining exercise with fasting is known to boost fat mass-loss, but detailed analysis on the consequential mobilization of visceral and subcutaneous WAT-derived fatty acids has not been performed. In this study, a subset of fasted male rats (66 h) was submitted to daily bouts of mild exercise. Subsequently, by using gas chromatography—flame ionization detection, the content of 22 fatty acids (FA) in visceral (v) versus subcutaneous (sc) white adipose tissue (WAT) depots was compared to those found in response to the separate events. Findings were related to those obtained in serum and liver samples, the latter taking up FA to increase gluconeogenesis and ketogenesis. Each separate intervention reduced scWAT FA content, associated with increased levels of adipose triglyceride lipase (ATGL) protein despite unaltered AMP-activated protein kinase (AMPK) Thr172 phosphorylation, known to induce ATGL expression. The mobility of FAs from vWAT during fasting was absent with the exception of the MUFA 16:1 n-7 and only induced by combining fasting with exercise which was accompanied with reduced hormone sensitive lipase (HSL) Ser563 and increased Ser565 phosphorylation, whereas ATGL protein levels were elevated during fasting in association with the persistently increased phosphorylation of AMPK at Thr172 both during fasting and in response to the combined intervention. As expected, liver FA content increased during fasting, and was not further affected by exercise, despite additional FA release from vWAT in this condition, underlining increased hepatic FA metabolism. Both fasting and its combination with exercise showed preferential hepatic metabolism of the prominent saturated FAs C:16 and C:18 compared to the unsaturated FAs 18:1 n-9 and 18:2 n-6:1. In conclusion, depot-specific differences in WAT fatty acid molecule release during fasting, irrelevant to their degree of saturation or chain length, are mitigated when combined with exercise, to provide fuel to surrounding organs such as the liver which is correlated with increased ATGL/ HSL ratios, involving AMPK only in vWAT.

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Caloric restriction prevents inflammation and insulin dysfunction in middle-aged ovariectomized mice

et al. 2023

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BackgroundLoss of ovarian function is associated with increased visceral fat. In this study, we aimed to study the effects of caloric restriction (CR) on metabolism in ovariectomized mice. Methods and ResultsFemale, 8-12-month-old mice were divided into three groups: OVX (ovariectomized mice), OVXR (40% CR) and Sham. CR increased insulin sensitivity and glucose tolerance. AMPK phosphorylation was observed in the liver of OVXR mice. CR also increased hepatic cholesterol and triglyceride levels. The reductions in the level of TBARS in the serum and liver and of H2O2 in the liver of OVXR mice suggested alterations in the redox state of the liver. Although expression of catalase protein was reduced by CR, expression of superoxide dismutase was not altered by CR. Although interleukin IL-6 and IL-10 levels in OVXR mice were similar to those in Sham mice, macrophage in ltration was reduced in OVXR mice.OVXR mice had increased sirtuin1 levels and decreased sirtuin3 levels in the liver. ConclusionsIn conclusion, CR improved the condition of ovariectomized mice by reducing adiposity and increasing insulin sensitivity and glucose tolerance through a mechanism that may involve AMPK.

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Both prolonged high-fat diet consumption and calorie restriction boost hepatic NAD+ metabolism in mice

Cited by 6 publications

References 62 publications

N1-methylnicotinamide impairs gestational glucose tolerance in mice

N1-methylnicotinamide impairs gestational glucose tolerance in mice

Exercise Equals the Mobilization of Visceral versus Subcutaneous Adipose Fatty Acid Molecules in Fasted Rats Associated with the Modulation of the AMPK/ATGL/HSL Axis

Caloric restriction prevents inflammation and insulin dysfunction in middle-aged ovariectomized mice

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