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NAD repletion with niacin counteracts cancer cachexia.

Cachexia is a debilitating wasting syndrome and highly prevalent comorbidity in cancer patients. It manifests especially with energy and mitochondrial metabolism aberrations that promote tissue wasting.

We recently identified nicotinamide adenine dinucleotide (NAD) loss to associate with muscle mitochondrial dysfunction in cancer hosts. In this study we confirm that depletion of NAD and downregulation of Nrk2, an NAD biosynthetic enzyme, are common features of severe cachexia in different mouse models.

Testing NAD repletion therapy in cachectic mice reveals that NAD precursor, vitamin B3 niacin, efficiently corrects tissue NAD levels, improves mitochondrial metabolism and ameliorates cancer- and chemotherapy-induced cachexia. In a clinical setting, we show that muscle NRK2 is downregulated in cancer patients.

The low expression of NRK2 correlates with metabolic abnormalities underscoring the significance of NAD in the pathophysiology of human cancer cachexia. Overall, our results propose NAD metabolism as a therapy target for cachectic cancer patients.

Sandra Zampieri

Rheumatology - Biochemistry

Azienda Ospedaliera di Padova

Italy

261

ScienceLeadR Reputation
profile photo of Sandra Zampieri

Main topics

Publications Clinical Trials

Autoimmune Diseases
Immune System Diseases
Muscular Diseases
Sarcopenia
Cachexia
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Fabio Penna

Biochemistry

University of Turin

Italy

241

ScienceLeadR Reputation
profile photo of Fabio Penna

Main topics

Publications Clinical Trials

Body Weight
Weight Loss
Cachexia
Sarcopenia
Heterocyclic Compounds
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Noora Pöllänen

Biochemistry

University of Helsinki

Finland

14

ScienceLeadR Reputation
profile photo of Noora Pöllänen

Main topics

Publications Clinical Trials

Cachexia
Heterocyclic Compounds
Niacinamide
Gonadal Hormones
Biological Science Disciplines
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Juha J Hulmi

Biochemistry

University of Jyväskylä

Finland

275

ScienceLeadR Reputation
profile photo of Juha J Hulmi

Main topics

Publications Clinical Trials

Gonadal Hormones
Physiology
Whey
Cachexia
Milk
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