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NAD+ is essential for whole-body fat burning (thermogenesis)

thermogenesis nmn mice adipose tissue bat wat

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#1 Fredrik

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Posted 09 November 2019 - 08:55 AM

This study was published in PNAS Nov 6 2019.
They used mice modified to lack NAMPT in either brown or both brown and white adipose tissue. But since NAMPT-activity decreases with age, NAD-repletion may bolster down-regulated whole-body energy metabolism via enhanced thermogenesis and lipolytic effects of fasting/CR, is my interpretation.
They administered NMN in drinking water at the approximate dose of 500 to 1000 mg/kg of body weight, to mice for up to 8 weeks. 
Non-shivering thermogenesis accounts for 20% of all the energy you burn in a day (B. Cannon, J. Nedergaard, Brown adipose tissue: Function and physiological significance. Physiol. Rev. 84, 277–359 (2004)). Keeping it high is important in obesitas prevention.
"Adipose tissue NAD+ biosynthesis is required for regulating adaptive thermogenesis and whole-body energy homeostasis in mice"

Thermogenesis is a fundamental aspect of energy homeostasis. Here, we present evidence that adipose tissue NAD + metabolism is essential for thermogenesis. 
We found cold exposure activates NAD + biosynthesis mediated by a rate-limiting enzyme, NAMPT, in mouse and human brown adipose tissue (BAT). Loss of NAMPT impairs the gene programs involved in thermogenesis and mitochondrial function in BAT. 
Mice lacking NAMPT in both BAT and white adipose tissue (WAT)[/b] but not in BAT alone [b]have impaired thermogenic responses to cold exposure, fasting, and β-adrenergic stimulation.
In WAT, NAMPT deletion decreases adrenergic-mediated lipolysis through inactivation of caveolin-1, which likely impairs whole-body thermogenesis. Nicotinamide mononucleotide administration normalized these metabolic derangements. 
These findings demonstrate the importance of adipose tissue NAD + biology in energy metabolism.




Taken together, these findings support the notion that NAD+ deficiency in WAT has important effects on whole-body metabolic function, particularly in people with obesity and older adults.
In conclusion, our data demonstrate that NAD+ is an essential regulator of adipose tissue metabolism and thermogenesis and illustrate the importance of adipocytes in regulating whole-body energy homeostasis.
The current commercial availability and increasing popularity of NAD+ boosters, such as NR and NMN, make it particularly important to further evaluate the translational potential of these experimental findings in rodents and cell systems to people and to determine whether NAD+ is a promising molecular target for enhancing adipose tissue function and whole-body energy homeostasis.




Edited by Fredrik, 09 November 2019 - 09:27 AM.

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Also tagged with one or more of these keywords: thermogenesis, nmn, mice, adipose tissue, bat, wat

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