Obesity—A Disease With Many Aetiologies Disguised in the Same Oversized Phenotype

Has the Overeating Theory Failed?

Peter Stenvinkel


Nephrol Dial Transplant. 2015;30(10):1656-1664. 

In This Article

Nutrients That Counter Insulin Resistance and Fat Accumulation

Plant phenols provide colour and taste to fruits, grapes and berries and include a large group of metabolites that include tannins, flavonoids (anthocyanins and flavonols) and stillbenoids. Polyphenols possess effects that counter obesity and obesity-related inflammation in animal studies.[56] Indeed, these nutrients lower triglycerides and body weight by increasing energy expenditure, increase fat utilization and modulate glucose homeostasis.[56] Moreover, cellular studies have shown that polyphenols suppress adipocyte differentiation, stimulate lipolysis and fatty-acid β-oxidation, reduce inflammation and the viability of pre-adipocytes by modulation of signalling pathways, such as AMPK, PPAR-γ, uncoupling proteins, PGC-1α and NF-κB. As resveratrol has beneficial effects on energy metabolism and mitochondrial oxidative capacity, this 'caloric restriction mimetic' may be a novel treatment for obese and insulin-resistant individuals.[57] Indeed, a study in rhesus monkeys on a high-fat and high-sugar diet showed that 2 years of resveratrol administration reduced the inflammatory response in adipose tissue.[58] Whereas animal studies clearly demonstrated a potential of resveratrol to improve metabolic health parameters and prevent obesity, studies in man have been conflicting. This could be due to differences in timing of the consumption of the drug, low bioavailability of resveratrol and the metabolic status of the study subjects.[59]

Vaccinium Berries Counter the Effects of a High-fat Diet

It is of interest that fibres and/or polyphenols present in lingonberries counteract the glycaemic effect of the sugars when consumed together with glucose.[60] Lingonberries were recently shown to have pronounced anti-obesity effects and they prevented the metabolic effects of a high-fat diet.[61] As blueberry polyphenols inhibit adipogenesis and cell proliferation,[62] it can be hypothesized that high intake of berries can counteract the negative outcomes of calorie-rich junk food. Indeed, in healthy subjects, consumption of berries improved the glycaemic control after sucrose ingestion,[63] and bilberry consumption reduced low-grade inflammation.[64] It could be speculated that the massive intake of berries (≈250 000 berries/day) during summer and fall counters the detrimental metabolic effects of insulin resistance and fat mass accumulation that bears develop in preparation for hibernation.[28]

Nuts—Energy Dense But With Beneficial Metabolic Effects

Although nuts are very rich in fat and calories, a recent meta-analysis showed that nut-rich diets did not increase body weight or BMI.[65] On the contrary, interventional studies have shown beneficial effects of nuts (especially walnuts) on the cardiometabolic profile[66] and endothelial function.[67] Actually, a recent study in 803 adults showed an inverse association between intake of tree nuts and obesity.[68] Whereas the high satiety index of nuts (resulting in reduced energy consumption, increased thermogenesis and fat malabsorption) could contribute to reduced risk of weight gain, also their richness in polyphenols, tocopherols, minerals, fibres and unsaturated fatty acids could contribute to their salutary effects.[69]

Nutrients That Stimulate Nrf2

The nuclear transcription factor Nrf2 is a key regulator of antioxidant pathways by activation of antioxidant genes. This has implications for mitochondrial biogenesis, lipid metabolism, insulin signalling and adipocyte differentiation and maturation.[70] Administration of Nrf2 activators protected mice from fat-induced obesity[71] and a randomized controlled trial of type 2 diabetic CKD Stage 4 patients showed that the Nrf2 agonist bardoxolone reduced body weight.[72] As several chemical compounds in food (such as polyphenols, resveratrol, cathecins, allicins, lycopene and caffeine) activate Nrf2,[73] it can be hypothesized that low intake of nutrients rich in Nrf2-stimulating chemicals could increase susceptibility to fat accumulation. In this respect, the reported positive effect of coffee intake on insulin sensitivity and weight loss is of interest.[74]

Fish Eaters Have Lower BMI

As fish eaters have been reported to have lower BMI than meat eaters,[75] the impact of marine lipids on insulin resistance and fat accumulation deserve attention. Although increased intake of marine lipids (i.e. omega-3 fatty acids) associates with improved mitochondrial function and anti-inflammatory effects, their impact on obesity development and progression has been inconclusive.[76] However, a study on dietary obese mice demonstrated that n-3 long-chain polyunsaturated fatty acids in combination with rosiglitazone preserved whole-body glucose utilization in skeletal muscle.[77] It has also been suggested that the beneficial impact of omega-3 phospholipids on adiponectin and leptin levels in obese patients may be of benefit in the prevention of weight gain during caloric restriction.[76]