Nutritional Modulation of AMPK-Impact upon Metabolic-Inflammation

Abstract

Nutritional status provides metabolic substrates to activate AMP-Activated Protein Kinase (AMPK), the energy sensor that regulates metabolism. Recent evidence has demonstrated that AMPK has wider functions with respect to regulating immune cell metabolism and function. One such example is the regulatory role that AMPK has on NLRP3-inlflammasome and IL-1β biology. This in turn can result in subsequent negative downstream effects on glucose, lipid and insulin metabolism. Nutrient stress in the form of obesity can impact AMPK and whole-body metabolism, leading to complications such as type 2 diabetes and cancer risk. There is a lack of data regarding the nature and extent that nutrient status has on AMPK and metabolic-inflammation. However, emerging work elucidates to a direct role of individual nutrients on AMPK and metabolic-inflammation, as a possible means of modulating AMPK activity. The posit being to use such nutritional agents to re-configure metabolic-inflammation towards more oxidative phosphorylation and promote the resolution of inflammation. The complex paradigm will be discussed within the context of if/how dietary components, nutrients including fatty acids and non-nutrient food components, such as resveratrol, berberine, curcumin and the flavonoid genistein, modulate AMPK dependent processes relating to inflammation and metabolism.

Keywords: AMPK; IL-1β; NLRP3; dietary fatty acids; metabolic-inflammation; nutrigenomics; nutrition.

Figure 1

The role of AMP-Activated Protein Kinase (AMPK) on whole-body metabolism. AMPK is a nutrient sensor, which is activated in response to low adenosine triphosphate (ATP) levels, and an increased adenosine diphosphate: adenosine monophosphate (ADP:AMP) ratio. As a result, it activates pathways that produce ATP through glucose, lipid and mitochondrial metabolism pathways, thus increasing ATP levels. Conversely, pathways that deplete ATP are inhibited by AMPK. An ↑ arrow represents an upregulation of the process and ↓ represents a downregulation of the process. AMPK = AMP-Activated Protein Kinase, ATP = Adenosine triphosphate, ADP = Adenosine diphosphate, AMP = Adenosine monophosphate.

Figure 2

Whole body AMPK modulation and the impact of different nutrients on AMPK activation. Excess nutrient consumption through high fat diet (HFD) and obesity can downregulate AMP-Activated Protein Kinase (AMPK) expression and cause dysregulated metabolism, inflammation and insulin resistance. Nutrients, including monounsaturated fatty acids (MUFA), α linoleic acid (ALA), berberine, resveratrol, curcumin and flavonoids can all activate AMPK and downstream positive effects in relation to improved mitochondrial metabolism, improved liver function and reduced inflammation. Therefore, modulation of AMPK through nutrient intervention can improve whole body metabolism. An ↑ arrow represents an upregulation of the process or increased expression and ↓ represents a downregulation of the process or decreased expression. AMPK = AMP-Activated Protein Kinase, MUFA = Monounsaturated fatty acids, OA = Oleic acid, PO = Palmitoleic acid, ALA = α linoleic acid, SREBP1 = Sterol regulatory element-binding protein 1c, FAO = fatty acid oxidation.