Precision Nutrition to Activate Thermogenesis as a Complementary Approach to Target Obesity and Associated-Metabolic-Disorders

Abstract

Obesity is associated to increased incidence and poorer prognosis in multiple cancers, contributing to up to 20% of cancer related deaths. These associations are mainly driven by metabolic and inflammatory changes in the adipose tissue during obesity, which disrupt the physiologic metabolic homeostasis. The association between obesity and hypercholesterolemia, hypertension, cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) is well known. Importantly, the retrospective analysis of more than 1000 epidemiological studies have also shown the positive correlation between the excess of fatness with the risk of cancer. In addition, more important than weight, it is the dysfunctional adipose tissue the main driver of insulin resistance, metabolic syndrome and all cause of mortality and cancer deaths, which also explains why normal weight individuals may behave as “metabolically unhealthy obese” individuals. Adipocytes also have direct effects on tumor cells through paracrine signaling. Downregulation of adiponectin and upregulation of leptin in serum correlate with markers of chronic inflammation, and crown like structures (CLS) associated to the adipose tissue disfunction. Nevertheless, obesity is a preventable risk factor in cancer. Lifestyle interventions might contribute to reduce the adverse effects of obesity. Thus, Mediterranean diet interventional studies have been shown to reduce to circulation inflammatory factors, insulin sensitivity and cardiovascular function, with durable responses of up to 2 years in obese patients. Mediterranean diet supplemented with extra-virgin olive oil reduced the incidence of breast cancer compared with a control diet. Physical activity is another important lifestyle factor which may also contribute to reduced systemic biomarkers of metabolic syndrome associated to obesity. In this scenario, precision nutrition may provide complementary approaches to target the metabolic inflammation associated to “unhealthy obesity”. Herein, we first describe the different types of adipose tissue -thermogenic active brown adipose tissue (BAT) versus the energy storing white adipose tissue (WAT). We then move on precision nutrition based strategies, by mean of natural extracts derived from plants and/or diet derived ingredients, which may be useful to normalize the metabolic inflammation associated to “unhealthy obesity”. More specifically, we focus on two axis: (1) the activation of thermogenesis in BAT and browning of WAT; (2) and the potential of augmenting the oxidative capacity of muscles to dissipate energy. These strategies may be particularly relevant as complementary approaches to alleviate obesity associated effects on chronic inflammation, immunosuppression, angiogenesis and chemotherapy resistance in cancer. Finally, we summarize main studies where plant derived extracts, mainly, polyphenols and flavonoids, have been applied to increase the energy expenditure.

Impact of the Level of Adherence to Mediterranean Diet on the Parameters of Metabolic Syndrome: A Systematic Review and Meta-Analysis of Observational Studies

“…MiRNAs were found to be better regulated in obese patients following an MD [ 137 ]. Recent studies have shown that an MD reduces serum inflammatory markers as well as the incidence of stroke, CVD and breast cancer [ 138 , 139 ]. Moreover, MD was recommended as a diet that can help women with menopause-related symptoms and needs [ 140 ].…”

The COVID-19 "Bad Tryp" Syndrome: NAD/NADH+, Tryptophan Phenylalanine Metabolism and Thermogenesis like Hecatomb - The Hypothesis of Pathophysiology Based on a Compared COVID-19 and Yellow Fever Inflammatory Skeleton

“…β3-AR signalling. The relative roles and modes of regulation of GLUT1 versus GLUT4-dependent glucose uptake in thermogenic fat in vivo will require further investigation [116,[137][138][139][140].…”

Adiponectin Modulation by Genotype and Maternal Choline Supplementation in a Mouse Model of Down Syndrome and Alzheimer’s Disease

“…We previously showed dysregulation within the T2DM pathway in male Ts mice compared to 2N littermates at~6 MO [75]. Accordingly, we used Fr Ctx tissue, which receives a prominent cholinergic input from BFCNs to interrogate three protein hormones dysregulated in human MetS/IR and T2DM: APN, insulin and leptin [30][31][32][33] in trisomic mice, with the hypothesis that MCS would have a beneficial effect. APN levels were significantly downregulated by approximately two-fold in Ts Fr Ctx (mean 9.53 ng/mL; p < 0.001; Figure 1A) compared to 2N (mean 18.89 ng/mL).…”

“…MetS/IR as well as T2DM are recognized as risk factors for dementia associated with AD [29]. The protein hormones insulin, leptin and adiponectin (APN) are linked to MetS/IR, T2DM and the associated increased risk for AD pathology [30][31][32][33]. Studies in persons with DS have also shown dysregulation of these protein hormones [24,34].…”