Posted by reCellorCircadian AM+PM
on November 17, 2025
Reading time: 10~12 minutes
Last Updated November 18, 2025
Obesity is far more complex than simply “eating too much and moving too little.” Modern research reveals that obesity is essentially a disorder of deep metabolic imbalance and disrupted circadian rhythm. At the center of this complex system lies a molecule that’s gaining increasing scientific attention—NAD⁺ (nicotinamide adenine dinucleotide).
You may have heard of NAD⁺ in relation to “aging,” “energy,” or “mitochondria,” but new research shows:
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Obesity itself significantly reduces NAD⁺ levels in the hypothalamus and metabolic organs
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Low NAD⁺ impairs the brain’s ability to regulate appetite and circadian rhythm, accelerating weight gain
And supplementing NAD⁺ may be the key to breaking this vicious cycle.
01Why Does Obesity Cause NAD⁺ Deficiency?
Studies show that high-fat diets (HFD) and obesity significantly reduce NAD⁺ levels across several tissues, especially:
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Liver, skeletal muscle, and white adipose tissue (key metabolic organs)
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The hypothalamus—the brain region controlling appetite, energy balance, and circadian rhythm
The paper clearly states:
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A high-fat diet sharply decreases hypothalamic NAD⁺
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This reduction suppresses SIRT1 and other NAD-dependent enzymes, disrupting neural regulatory systems
In other words, the heavier the body becomes, the more it traps itself in a loop of:
Reduced energy expenditure → Increased appetite → Reduced physical activity → Continued weight gain
And at the center of this vicious cycle is NAD⁺ depletion.
02What Happens When You Supplement NAD⁺?
The Study Gives Clear Answers
The study used exogenous NAD⁺ injections (1 mg/kg/day for 4 weeks), and the results were remarkable:
Despite the dose being far lower than common NMN/NR doses (100–500 mg/kg),NAD⁺ supplementation still produced significant benefits.
① It significantly suppressed weight gain
Compared with untreated obese mice, those receiving NAD⁺ gained weight much more slowly.This is one of the study’s most important findings.
② It increased energy expenditure (EE)
Obese mice normally show reduced EE, but NAD⁺ supplementation led to:
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A notable increase in nighttime EE (the active period for mice)
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Overall 24-hour metabolic activity improvement
This means the body’s natural fat-burning ability was enhanced.
③ It increased locomotor activity
The study showed:
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Obese mice had lower activity levels, especially at night
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With NAD⁺ supplementation, their activity levels fully returned to those of lean mice
This isn’t a stimulant-like effect—it’s a restoration of physiological rhythm.
④ It reduced appetite and restored normal eating patterns
Obesity causes:
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Excessive daytime eating
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Frequent small meals throughout the day (increased feeding bouts)
After NAD⁺ supplementation:
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Daytime calorie intake dropped significantly
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Feeding frequency returned to normal (no more fragmented eating)
This indicates that NAD⁺ improves hypothalamic appetite regulation.
03 Why Does NAD⁺ Affect Body Weight?
The Key Lies in the Hypothalamus and Circadian Rhythm
One major contribution of the study is revealing the relationship between NAD⁺ and the clock gene PER1.
● Obesity flattens PER1 day–night oscillation—your body loses its natural rhythm
In lean mice, PER1 levels rise and fall dramatically across day and night.
In obese mice, this rhythmic oscillation is “flattened,” indicating circadian dysfunction.
● NAD⁺ supplementation fully restores PER1 oscillation
The study found that:
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NAD⁺ restores normal PER1 day–night oscillation in the ARC (the hypothalamic region controlling appetite)
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This helps re-establish the body’s internal signal for when to eat and when not to eat
This is the deep mechanism behind NAD⁺’s ability to improve appetite control and eating patterns.
● NAD⁺ = fuel for the circadian clock
NAD⁺ enhances CLOCK/BMAL1 activation of PER1
and reverses the suppression of PER1 caused by NAD⁺ depletion.
In short:
Low NAD⁺ → circadian disorder → increased appetite neuropeptides → easier weight gain Restored NAD⁺ → circadian normalization → better appetite control
04 NAD⁺ Also Regulates Key Appetite Neuropeptides: NPY and AgRP
NPY and AgRP are “hunger-driving” neuropeptides in the brain.
The study shows:
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NAD⁺ deficiency → NPY/AgRP activity increases (more hunger)
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NAD⁺ supplementation → suppresses NPY/AgRP and restores normal rhythm
NPY and AgRP also correlate positively with PER1:
The more disrupted the circadian rhythm, the stronger the drive to overeat.
This explains why:
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Many people with obesity sleep poorly
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Feel hungrier during the day
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Experience stronger cravings at night
05 Why Is NAD⁺ Supplementation Necessary?
Based on key findings of the study:
① Obesity itself greatly reduces NAD⁺ levels
Especially in the hypothalamus, affecting appetite, metabolism, and circadian rhythm.
② NAD⁺ is essential for metabolic, appetite, and circadian stability
It is the “fuel” for SIRT1, CLOCK/BMAL1, and other core regulators.
③ Diet, exercise, and genetics alone cannot quickly restore NAD⁺
Obesity-induced NAD⁺ depletion is a persistent metabolic issue.
④ NAD⁺ supplementation acts on multiple pathways simultaneously:
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↑ Energy expenditure
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↑ Physical activity
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↓ Caloric intake
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↓ Hunger neuropeptides
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↑ Circadian rhythm stability
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↓ Weight gain
This forms a multi-target, systemic anti-obesity mechanism.
06 Conclusion:
NAD⁺—More Than “Anti-Aging,” It’s a Central Key to Metabolic Health
This study highlights an overlooked fact:
One root cause of obesity is NAD⁺ depletion and disrupted metabolic circadian rhythm.
Supplementing NAD⁺
not only restores metabolic efficiency,
but also helps the body regain its natural rhythm:
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When to eat
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When to move
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When to rest
For individuals with obesity, metabolic disorders, or circadian rhythm disruption, NAD⁺ supplementation carries meaningful physiological value and therapeutic potential.
References
Roh, E., Kang, G. M., Gil, S. Y., Lee, C. H., Kim, S., Hong, D., ... Kim, M. S. (2018). Effects of chronic NAD supplementation on energy metabolism and diurnal rhythm in obese mice. Obesity (Silver Spring), 26(9), 1448-1456. https://doi.org/10.1002/oby.22263
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.
