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Background and ObjectiveWhile underlying pathophysiology linking obesity to brain health is not completely understood, white adipose tissue (WAT) is considered a key player. In obesity, WAT becomes dysregulated, showing hyperplasia, hypertrophy, and eventually inflammation. This disbalance leads to dysregulated secretion of adipokines influencing both (cardio)vascular and brain health. Within this study, we investigated the association between omental WAT (oWAT) and subcutaneous WAT (scWAT) with brain structure and perfusion and cognition in adults with severe obesity.MethodsWithin the cross-sectional BARICO study, brain structure and perfusion and cognitive function were measured before bariatric surgery (BS) using MRI and cognitive assessments. During BS, oWAT and scWAT depots were collected and analyzed by histopathology. The number and diameter of adipocytes were quantified together with the amount of crown-like structures (CLS) as an indication of inflammation. Blood samples were collected to analyze adipokines and inflammatory markers. Neuroimaging outcomes included brain volumes, cortical thickness, white matter (WM) integrity, WM hyperintensities, cerebral blood flow using arterial spin labeling (ASL), and the ASL spatial coefficient of variation (sCoV), reflecting cerebrovascular health.ResultsSeventy-one patients were included (mean age 45.1 ± 5.8 years; 83.1% women; mean body mass index 40.8 ± 3.8 kg/m2). scWAT showed more CLS (z= −2.72,p< 0.01,r= −0.24) and hypertrophy compared with oWAT (F(1,64) = 3.99,p< 0.05, η2= 0.06). Adiponectin levels were inversely associated with the average diameter of scWAT (β = −0.31, 95% CI −0.54 to −0.08) and oWAT (β = −0.33, 95% CI −0.55 to −0.09). Furthermore, the adipocyte diameter in oWAT was positively associated with the sCoV in the parietal cortex (β = 0.33, 95% CI 0.10–0.60), and the number of adipocytes (per mm2) was positively associated with sCoV in the nucleus accumbens (NAcc) (β = 0.34, 95% CI 0.09–0.61). Cognitive function did not correlate with any WAT parameter or plasma marker. These associations were highly influenced by age and sex. sCoV in the NAcc was positively associated with fasting plasma glucose (β = 0.35, 95% CI 0.10–0.56).DiscussionscWAT and oWAT are different in morphology and in their relationship with plasma markers and cerebrovascular health. Although scWAT showed more CLS and hypertrophy, scWAT was not associated with brain readouts. This study showed, however, important relationships between oWAT morphology and cerebrovascular health in obesity.Trial Registration InformationTrial Registration Number NTR7288 (trialregister.nl/trial/7090).

Obesity characterized by adiposity and ectopic fat accumulation is associated with the development of non-alcoholic fatty liver disease (NAFLD). Treatments that stimulate lipid utilization may prevent the development of obesity and comorbidities. This study evaluated the potential anti-obesogenic hepatoprotective effects of combined treatment with L-carnitine and nicotinamide riboside, i.e., components that can enhance fatty acid transfer across the inner mitochondrial membrane and increase nicotinamide adenine nucleotide (NAD+) levels, which are necessary for &beta, oxidation and the TCA cycle, respectively. Ldlr &minus, /&minus, Leiden mice were treated with high-fat diet (HFD) supplemented with L-carnitine (LC, 0.4% w/w), nicotinamide riboside (NR, 0.3% w/w) or both (COMBI) for 21 weeks. L-carnitine plasma levels were reduced by HFD and normalized by LC. NR supplementation raised its plasma metabolite levels demonstrating effective delivery. Although food intake and ambulatory activity were comparable in all groups, COMBI treatment significantly attenuated HFD-induced body weight gain, fat mass gain (&minus, 17%) and hepatic steatosis (&minus, 22%). Also, NR and COMBI reduced hepatic 4-hydroxynonenal adducts. Upstream-regulator gene analysis demonstrated that COMBI reversed detrimental effects of HFD on liver metabolism pathways and associated regulators, e.g., ACOX, SCAP, SREBF, PPARGC1B, and INSR. Combination treatment with LC and NR exerts protective effects on metabolic pathways and constitutes a new approach to attenuate HFD-induced obesity and NAFLD.