Human study finds high-fat food decreases SIRT1 & 6 and increases SIRT4 levels, establishes link to disease and obesity

Typical western diets consist of poor food choices over a lifetime that can contribute to diet-induced obesity, systemic inflammation and a variety of other pathological conditions. A key characteristic of obesity is low-grade inflammation, which initially originates in the adipose tissue. Adipose tissue inflammation is mediated by cytokines, chemokines, and potentially sirtuins (SIRT). There are 7 SIRTs, each with different functions but many associated with metabolism and inflammation. With regard to inflammation, SIRTs may epigenetically reprogram leukocytes, alter NF-kβ translocation, and/or alter upstream signaling associated with pro-inflammatory cytokine production depending on the state of nutrients available

Sirtuins are nicotinamide adenosine dinucleotide (NAD+) dependent and known to be more active in periods of restricted calorie intake. At the same time it is known that consumption of a high-fat meal increases systemic inflammation and CVD disease risk biomarkers. Studies in mice models have shown that sirtuin activity is inhibited after consumption of a high-fat meal. The researchers in this study investigated whether a high-fat, high-caloric meal altered the expression of sirtuins in humans.

The researchers recruited twelve men and twelve women, between eighteen and thirty-five years of age for the study. All were of normal body weight and average fitness level. All subjects were considered “apparently healthy”, non-smokers and not taking any medications. The men and women had 20-min to consume the high-fat commercial meal on the morning of the testing day. Once the meal was consumed, blood samples were collected at 1, 3, and 5-h.

The researchers found that SIRT1 and SIRT6 expression decreased and that SIRT4 expression increased within 3-5 hours after the meal. The SIRT1 and SIRT6 observations correlate to the observed fat diet disease consequences like regulate inflammatory processes, via alterations in NF-ƙB translocation. The SIRT4 increase  at 5-h post meal consumption could be due to its capacity to repress fatty acid oxidation and stimulate lipogenesis. Its  likely that this over expression of SIRT4 at 5-h post meal was contributing to an increase deposits of triglycerides in the adipose tissue.

The researchers also speculated that because at the 5-h post meal the SIRT expression levels had not returned to baseline values that consecutive high-fat meals in one day or consecutive days may result in long periods of decreased SIRT1 and SIRT6 and increase in SIRT4 activity that would contribute to systemic inflammation, obesity, cardiovascular and metabolic diseases.

It was also observed that there were strong correlations between baseline mRNA expression of SIRTs and the postmeal triglyceride response as a possible mechanism for the altered SIRT levels.

In summary this study demonstrated a SIRT related mechanism for the health as consequences of consuming high fat meals in humans, confirming similar obeservations in mice models . Based on that the researchers also pointed out that this supports the notion that sirtuin enablers and activators could have a beneficial health effect in preventing and treating obesity. While not speciafically mentioned nicotinamide riboside and pterostilbene are examples of such activators. Obviously establishing a healthy diet is the first thing to do.

You can find the study here.

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