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

Science ◽  
2021 ◽  
Vol 373 (6554) ◽  
pp. eabj1696
Author(s):  
Charles Brenner

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.

2020 ◽  
Author(s):  
Oana P. Zaharia ◽  
Klaus Strassburger ◽  
Birgit Knebel ◽  
Yuliya Kupriyanova ◽  
Yanislava Karusheva ◽  
...  

<a><b>Objective</b></a>: The rs738409(G) single-nucleotide polymorphism (SNP) in the patatin-like phospholipase domain-containing 3 (<i>PNPLA3</i>) 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. <p><b>Research Design and Methods</b>: A total of 917 participants of the German Diabetes Study underwent genotyping, hyperinsulinemic-euglycemic clamps with stable isotopic tracer dilution and magnetic resonance spectroscopy. </p> <p><b>Results:</b> 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 <i>PNPLA3</i> 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).</p> <b>Conclusions:</b> 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.


Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 5-LB
Author(s):  
DESIREE SIGALA ◽  
BETTINA HIERONIMUS ◽  
CANDICE PRICE ◽  
VIVIEN LEE ◽  
MARINELLE NUNEZ ◽  
...  

2003 ◽  
Vol 112 (6) ◽  
pp. 935-944 ◽  
Author(s):  
Michihiro Matsumoto ◽  
Wataru Ogawa ◽  
Kazunori Akimoto ◽  
Hiroshi Inoue ◽  
Kazuaki Miyake ◽  
...  

2020 ◽  
Author(s):  
Oana P. Zaharia ◽  
Klaus Strassburger ◽  
Birgit Knebel ◽  
Yuliya Kupriyanova ◽  
Yanislava Karusheva ◽  
...  

<a><b>Objective</b></a>: The rs738409(G) single-nucleotide polymorphism (SNP) in the patatin-like phospholipase domain-containing 3 (<i>PNPLA3</i>) 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. <p><b>Research Design and Methods</b>: A total of 917 participants of the German Diabetes Study underwent genotyping, hyperinsulinemic-euglycemic clamps with stable isotopic tracer dilution and magnetic resonance spectroscopy. </p> <p><b>Results:</b> 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 <i>PNPLA3</i> 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).</p> <b>Conclusions:</b> 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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Timea Kurdiova ◽  
Miroslav Balaz ◽  
Zuzana Kovanicova ◽  
Erika Zemkova ◽  
Martin Kuzma ◽  
...  

AimAfamin is a liver-produced glycoprotein, a potential early marker of metabolic syndrome. Here we investigated regulation of afamin in a course of the metabolic disease development and in response to 3-month exercise intervention.MethodsWe measured whole-body insulin sensitivity (euglycemic hyperinsulinemic clamp), glucose tolerance, abdominal adiposity, hepatic lipid content (magnetic resonance imaging/spectroscopy), habitual physical activity (accelerometers) and serum afamin (enzyme-linked immunosorbent assay) in 71 middle-aged men with obesity, prediabetes and newly diagnosed type 2 diabetes. Effects of 3-month exercise were investigated in 22 overweight-to-obese middle-aged individuals (16M/6F).ResultsPrediabetes and type 2 diabetes, but not obesity, were associated with increased serum afamin (p&lt;0.001). Afamin correlated positively with hepatic lipids, fatty liver index and liver damage markers; with parameters of adiposity (waist circumference, %body fat, adipocyte diameter) and insulin resistance (fasting insulin, C-peptide, HOMA-IR; p&lt;0.001 all). Moreover, afamin negatively correlated with whole-body insulin sensitivity (M-value/Insulin, p&lt;0.001). Hepatic lipids and fasting insulinemia were the most important predictors of serum afamin, explaining &gt;63% of its variability. Exercise-related changes in afamin were paralleled by reciprocal changes in insulinemia, insulin resistance and visceral adiposity. No significant change in hepatic lipid content was observed.ConclusionsSubjects with prediabetes and type 2 diabetes had the highest serum afamin levels. Afamin was more tightly related to hepatic lipid accumulation, liver damage and insulin resistance than to obesity.


2018 ◽  
Vol 315 (2) ◽  
pp. E218-E228 ◽  
Author(s):  
Difei Wang ◽  
Huiying Cong ◽  
Xiaoli Wang ◽  
Yanli Cao ◽  
Shoichiro Ikuyama ◽  
...  

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).


2018 ◽  
Vol 101 (2) ◽  
pp. 1379-1387 ◽  
Author(s):  
M.M. Fry ◽  
B. Yao ◽  
C. Ríos ◽  
C. Wong ◽  
S. Mann ◽  
...  

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1906-P
Author(s):  
AMY M. GOSS ◽  
SHIMA DOWLA ◽  
AMBIKA P. ASHRAF ◽  
MARK BOLDING ◽  
SHANNON A. MORRISON ◽  
...  

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