Domesticated in 8000–10,000 BP in northern China, proso millet (Panicum miliaceum L.) is the best adaptive rotational crop for semiarid central High Plains of the USA, where average annual precipitation is 356–407 mm. Proso millet has multiple benefits when consumed as human food. Proso millet is rich in minerals, dietary fiber, polyphenols, vitamins and proteins. It is gluten-free and therefore, ideal for the gluten intolerant people. Proso millet contains high lecithin which supports the neural health system. It is rich in vitamins (niacin, B-complex vitamins, folic acid), minerals (P, Ca, Zn, Fe) and essential amino acids (methionine and cysteine). It has a low glycemic index and reduces the risk of type-2 diabetes. Unfortunately, in the USA, it is mostly considered as bird feed, whereas it is mainly used as human food in many other countries. Besides human health benefits, proso millet has an impeccable environmental benefit. Proso millet possesses many unique characteristics (e.g., drought tolerance, short-growing season) which makes it a promising rotational crop for winter wheat-based dryland farming systems. Proso millet provides the most economical production system when used in a two years wheat/summer fallow cropping system in semiarid High Plains of the USA. It helps in controlling winter annual grass weeds, managing disease and insect pressure and preserving deep soil moisture for wheat. Proso millet can also be used as a rotational crop with corn or sorghum owing to its tolerance for atrazine, the primary herbicide used in corn and sorghum production systems. Proso millet certainly is a climate-smart, gluten-free, ancient, and small grain cereal, which is healthy to humans and the environment. The main challenge is to expand the proso millet market beyond bird feed into the human food industry. To overcome the challenge, unique proso millet varieties for human food and ready-to-use multiple food products must be developed. This requires successful collaboration among experts from diverse disciplines such as breeders, geneticists, food chemists and food industry partners.

T he human gastrointestinal tract is populated with at least 100 trillion bacteria that provide their host with dietary metabolites. Extensive studies have demonstrated that human gut microbiota affect energy balance, gut permeability, serum lipopolysaccharides levels, and metabolic inflammation associated with obesity and diabetes mellitus.1 Subjects with obesity and type 2 diabetes mellitus are characterized by altered gut microbiota, inflammation, and gut barrier disruption. In addition, the population of beneficial gut bacteria has been found to be reduced in animal models of metabolic syndrome. For instance, the abundance of a beneficial gut bacterium, Akkermansia muciniphila (A muciniphila), is significantly lower in the genetically obese ob/ob mice or mice fed a high-fat diet compared with their lean littermates. Increased colonization of A muciniphila has also been found to be capable of reversing high-fat diet-induced metabolic disorders.2 In contrast, disease-promoting gut bacteria induce metabolic disorders. For instance, a strain of the Enterobacter cloacae, B29, isolated from a morbidly obese human, induced obesity and insulin resistance in a rodent model, and the severity of disease was found to be closely related to the lipid content in the diet. 3A muciniphila is a mucin-degrading bacterium that resides in the mucus layer of intestine, and it abundantly colonizes in this nutrient-rich environment. 4 Oral administration of live A muciniphila has been shown to prevent diet-induced obesity by altering adipose tissue metabolism and gut permeability without affecting food intake.2 However, the regulatory effect of A muciniphila on host lipid metabolism, particularly on hepatic lipid signaling and lipoprotein metabolism, is unexplored.© 2016 American Heart Association, Inc. Objective-Akkermansia muciniphila (A muciniphila) is a mucin-degrading bacterium that resides in the mucus layer whose abundance inversely correlates with body weight and the development of diabetes mellitus in mice and humans. The objective of this study was to explore the regulatory effect of A muciniphila on host lipoprotein metabolism, insulin sensitivity, and hepatic metabolic inflammation. Approach and Results-By establishing a novel mouse model that colonized the A muciniphila in the gastrointestinal tract of the cAMP-responsive binding protein H (CREBH)-deficient mouse and in vivo chylomicron assay, we found that increased colonization of A muciniphila in the gastrointestinal tract of wild-type mice protected mice from an acute fat load-induced hyperlipidemia compared with vehicle-treated mice. A muciniphila administration also significantly ameliorated chronic hypertriglyceridemia, improved insulin sensitivity, and prevented overproduction of postprandial chylomicrons in CREBH-null mice. Mechanistic studies revealed that increased A muciniphila colonization induced expression of low-density lipoprotein receptors and apolipoprotein E in the hepatocytes of CREBH-null mice, which facilitated the uptake of intermediate-density...

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Metabolic inflammation is closely associated with hyperlipidemia and cardiovascular disease. However, the underlying mechanisms are not fully understood. The current study established that cAMP-responsive-element-binding protein H (CREBH), an acute-phase transcription factor, enhances very-low-density lipoprotein (VLDL) assembly and secretion by upregulating apolipoprotein B (apoB) expression, and contributes to metabolic inflammation-associated hyperlipoproteinemia induced by TNFα, lipopolysaccharides (LPS), and a high-fat diet (HFD) in mice. Specifically, overexpression of CREBH significantly induced mRNA and protein expression of apoB in McA-7777 cells. Luciferase assay further revealed that the presence of CREBH could significantly increase the activities of the apoB gene promoter. In contrast, genetic depletion of CREBH in mice resulted in significant reduction in expression of hepatic apoB mRNA. Challenging mice with an acute fat load led to upregulation of triglyceride (TG)-rich lipoprotein secretion in wildtype mice, but not in CREBH-null mice. TNFα treatment activated hepatic CREBH expression, which in turn enhanced hepatic apoB biosynthesis and VLDL secretion. Metabolic inflammation induced by LPS or HFD also resulted in overproduction of apoB and hyperlipoproteinemia in wildtype mice, but not in CREBH-null mice. This study demonstrates that CREBH could be a mediator between metabolic inflammation and hepatic VLDL overproduction in chronic metabolic disorders. This novel finding establishes CREBH as the first transcription factor that regulates apoB expression on the transcriptional level and the subsequent VLDL biosynthesis in response to metabolic inflammation. The study also provides novel insight into the pathogenesis of hyperlipidemia in metabolic syndrome.