NR Boosts Fat-Burning Activity in Obese Mice

This study explored how increasing levels of NAD+ can improve the function of brown adipose tissue (BAT), a specialized "fat-burning" tissue, and counteract the negative effects of obesity.


What is Brown Fat and Why is it Important?

Brown fat, or brown adipose tissue (BAT), is a special type of body fat that burns energy to produce heat - unlike white fat, which stores energy. It’s rich in mitochondria, the “power plants” of our cells, which give brown fat its color and unique fat-burning ability.

Why it matters:

  • Brown fat helps regulate body temperature - especially in cold environments
  • It boosts metabolism and may protect against obesity and diabetes
  • As we gain weight or age, brown fat becomes less active and starts to “whiten,” losing its energy-burning function

Keeping brown fat healthy could be a powerful tool for improving metabolic health and fighting obesity.

Key Points

  • Obesity disrupted NAD+ production in BAT, leading to damaged mitochondria and reduced ability to burn energy 

  • Increasing NAD+ levels in obese mice improved the function of mitochondria in BAT

  • NR increased BAT activity, reduced fat accumulation, and improved metabolic health in obese mice

Study Overview

Researchers used databases of genetic information from different strains of mice to identify genes and proteins related to NAD+ production and BAT function.

They then conducted an 8-week experiment in male C57BL/6J mice fed a high-fat diet (HFD), comparing three groups:

  • Control (standard diet)

  • Obese (HFD)

  • Obese + NR (HFD + nicotinamide riboside at 400 mg/kg/day)

They measured NAD+ levels, mitochondrial function (via respirometry and imaging), thermogenic markers, and metabolic traits like body weight and oxygen consumption.

Obesity Impaired NAD+ Production and Mitochondrial Function

Obese mice showed reduced expression of enzymes critical for NAD+ production (Nampt and NMNat3). 

This was associated with impaired mitochondrial structure and function, increased fat accumulation, and lower physical performance.

NAD+ Replenishment Restored Mitochondrial Function

NR treatment raised NAD+ levels in brown fat and improved mitochondrial health and function: 

  • Increased energy production

  • Reduced markers of mitochondrial damage

  • Improved mitochondrial structure in BAT.

Microscopic images confirmed healthier, more intact mitochondria in NR-treated mice.

“The restoration of mitochondrial elongated shape after NR treatment is indicative of organelle function preservation.”

NR Enhanced Energy Expenditure and Reduced Obesity  

NR-treated mice had:

  • Higher body heat production

  • Elevated respiratory exchange ratio (RER), indicating better use of carbohydrates and fats

  • Increased expression of thermogenic proteins (UCP1, CPT1A, PRDM16)

  • Less weight gain and reduced fat accumulation, despite similar food intake

NR also preserved the brown color and structure of BAT, preventing the “whitening” typically seen in obesity.

“These findings support the potential of NR as a promising metabolic intervention capable of modulating thermogenesis and alleviating the deleterious effects of obesity on mitochondrial function in BAT.”

This figure summarizes the study. It contrasts the effects of a high-fat diet (left, red) with the effects of NR supplementation (right, green) on brown fat in mice. 

  • Obesity, induced by the high-fat diet, leads to reduced NAD+ levels, damaged mitochondria, impaired heat production, and a loss of brown fat's normal color ("whitening"). 

  • NR supplementation reverses these effects, preserving NAD+ levels, improving mitochondrial health, increasing heat production, and maintaining brown fat's normal color.

Conclusion 

This study suggests that boosting NAD+ levels with NR supplementation can counteract the harmful effects of obesity on brown adipose tissue, improving its ability to burn energy and reduce fat accumulation.  

“The oral treatment with nicotinamide riboside (NR), an NAD+ precursor, significantly boosted NAD+ levels and preserved the morphofunctional mitochondria aspects of mitochondria, and the thermogenesis capacity of BAT in HFD-fed mice.”

These findings indicate that targeting NAD+ metabolism may offer a potential strategy for treating obesity and related metabolic conditions.



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Dr. Rebecca Crews

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Leading the company’s engagement in transformative research. She is committed to scientific integrity in the health and wellness space and data transparency with consumers.

She holds a Ph.D. in Biochemical and Molecular Nutrition from Tufts University and has over ten years of nutrition science research experience, exploring various dimensions of human well-being in academic and government laboratories.