A5027318749- Adipose Tissue and Metabolism
- Sirtuins and Resveratrol in Medicine
- Polyamine Metabolism and Applications
- Mitochondrial Function and Pathology
- Cannabis and Cannabinoid Research
- Diet and metabolism studies
- Autophagy in Disease and Therapy
- Pancreatic function and diabetes
- Amino Acid Enzymes and Metabolism
- PARP inhibition in cancer therapy
- Metabolism, Diabetes, and Cancer
- Epigenetics and DNA Methylation
- Calcium signaling and nucleotide metabolism
- Diet, Metabolism, and Disease
- Liver Disease Diagnosis and Treatment
- Muscle metabolism and nutrition
- Muscle Physiology and Disorders
- Cytomegalovirus and herpesvirus research
- Nutrition and Health in Aging
- Genetic Neurodegenerative Diseases
- Cardiovascular Disease and Adiposity
- Cancer, Hypoxia, and Metabolism
- Hematopoietic Stem Cell Transplantation
- Metabolomics and Mass Spectrometry Studies
- Blood disorders and treatments
University of Oulu
2022-2025
University of Helsinki
2016-2025
Oulu University Hospital
2023-2025
École Polytechnique Fédérale de Lausanne
2011-2019
University of Eastern Finland
1999-2014
Institute for Molecular Medicine Finland
2014
Finland University
2009
Abstract Nutrient availability is the major regulator of life and reproduction, a complex cellular signaling network has evolved to adapt organisms fasting. These sensor pathways monitor energy metabolism, especially mitochondrial ATP production NAD + / NADH ratio, as signals for nutritional state. We hypothesized that these would be modified by respiratory chain disease, because inefficient utilization production. Oral administration nicotinamide riboside ( NR ), vitamin B3 precursor, was...
Mitochondrial disorders are highly heterogeneous conditions characterized by defects of the mitochondrial respiratory chain. Pharmacological activation biogenesis has been proposed as an effective means to correct biochemical and ameliorate clinical phenotype in these severely disabling, often fatal, disorders. Pathways related targets Sirtuin1, a NAD+-dependent protein deacetylase. As NAD+ boosts activity Sirtuin1 other sirtuins, intracellular levels play key role homeostatic control...
Nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide riboside (NR) has emerged as a promising compound to improve obesity-associated mitochondrial dysfunction and metabolic syndrome in mice. However, most short-term clinical trials conducted so far have not reported positive outcomes. Therefore, we aimed determine whether long-term NR supplementation boosts biogenesis health humans. Twenty body mass index (BMI)-discordant monozygotic twin pairs were supplemented with an escalating...
Sirtuins (SIRTs) regulate cellular metabolism and mitochondrial function according to the energy state of cell reflected by NAD(+) levels.Our aim was determine whether expressions SIRTs biosynthesis genes are affected acquired obesity how possible alterations connected with metabolic dysfunction while controlling for genetic familial factors.We studied a cross-sectional sample 40 healthy pairs monozygotic twins, including 26 who were discordant body mass index (within-pair difference > 3...
Sirt3 is a mitochondrial sirtuin, predominantly expressed in highly metabolic tissues. Germline ablation of has major consequences, including increased susceptibility to damage and oxidative stress after high fat feeding. In order determine the contribution liver skeletal muscle these phenotypes, we generated muscle-specific (Sirt3skm−/−) liver-specific (Sirt3hep−/−) knock-out mice. Despite marked global hyperacetylation proteins, Sirt3skm−/− Sirt3hep−/− mice did not manifest any overt...
Recent preclinical studies showed the potential of nicotinamide adenine dinucleotide (NAD+) precursors to increase oxidative phosphorylation and improve metabolic health, but human data are lacking. We hypothesize that nicotinic acid derivative acipimox, an NAD+ precursor, would directly affect mitochondrial function independent reductions in nonesterified fatty (NEFA) concentrations. In a multicenter randomized crossover trial, 21 patients with type 2 diabetes (age 57.7 ± 1.1 years, BMI...
Cachexia is a debilitating wasting syndrome and highly prevalent comorbidity in cancer patients. It manifests especially with energy mitochondrial metabolism aberrations that promote tissue wasting. We recently identified nicotinamide adenine dinucleotide (NAD+) loss to associate muscle dysfunction hosts. In this study we confirm depletion of NAD+ downregulation Nrk2, an biosynthetic enzyme, are common features severe cachexia different mouse models. Testing repletion therapy cachectic mice...
The intestinal epithelium has a high turnover rate and constantly renews itself through proliferation of crypt cells, which depends on insufficiently characterized signals from the microenvironment. Here, we showed that colonic macrophages were located directly adjacent to epithelial cells in mice, where they metabolically supported cell an mTORC1-dependent manner. Specifically, deletion tuberous sclerosis complex 2 (Tsc2) activated mTORC1 signaling protected against colitis-induced damage...
Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha) is an attractive candidate gene for type 2 diabetes, as genes of the oxidative phosphorylation (OXPHOS) pathway are coordinatively downregulated by reduced expression PGC-1 in skeletal muscle and adipose tissue patients with diabetes. Here we demonstrate that transgenic mice activated polyamine catabolism due to overexpression spermidine/spermine N(1)-acetyltransferase (SSAT) had white (WAT) mass, high basal...
<h3>Objective</h3> No therapy for non-alcoholic steatohepatitis (NASH) has been approved so far. Roux-en-y gastric bypass (RYGB) is emerging as a therapeutic option, although its effect on NASH and related hepatic molecular pathways unclear from human studies. We studied the of RYGB pre-existent mitochondrial dysfunction—a key player in pathogenesis—in novel diet-induced mouse model nicely mimicking disease. <h3>Design</h3> C57BL/6J mice were fed high-fat high-sucrose diet (HF-HSD)....
Sirtuins (SIRTs) and poly(ADP-ribose) polymerases (PARPs) are 2 important nicotinamide adenine dinucleotide (NAD)(+)-dependent enzyme families with opposing metabolic effects. Energy shortage increases NAD(+) biosynthesis SIRT activity but reduces PARP in animals. Effects of energy balance on these pathways humans unknown.We compared NAD(+)/SIRT pathway expressions activities sc adipose tissue (SAT) between lean obese subjects investigated their change the during a 12-month weight loss.SAT...
Abstract Background & aims We have previously reported that the serum levels of gut-derived tryptophan metabolite indole-3-propionic acid (IPA) are lower in individuals with liver fibrosis. Now, we explored transcriptome and DNA methylome associated IPA human from obese together effects on shifting hepatic stellate cell (HSC) phenotype to inactivation vitro. Methods A total 116 without type 2 diabetes (T2D) (age 46.8 ± 9.3 years; BMI: 42.7 5.0 kg/m ) Kuopio OBesity Surgery (KOBS) study...
PPARγ-dependent gene expression during adipogenesis is facilitated by ADP-ribosyltransferase D-type 1 (ARTD1; PARP1)-catalyzed poly-ADP-ribose (PAR) formation. Adipogenesis accompanied a dynamic modulation of the chromatin landscape at PPARγ target genes ligand-dependent co-factor exchange. However, how endogenous ligands, which have low affinity for receptor and are present levels in cell, can induce sufficient exchange unknown. Moreover, significance PAR formation PPARγ-regulated adipose...
Nonalcoholic fatty liver disease is one of the most prevalent metabolic disorders and it tightly associates with obesity, type 2 diabetes, cardiovascular disease. Reduced mitochondrial lipid oxidation contributes to hepatic acid accumulation. Here, we show that Fas cell surface death receptor (Fas/CD95/Apo-1) regulates metabolism. Hepatic overexpression in chow-fed mice compromises oxidation, respiration, abundance respiratory complexes promoting accumulation insulin resistance. In line,...