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Proso millet (Panicum miliaceum L.) is one of the seven commonly cultivated millets. It is regarded as a climate-smart, ancient, and gluten-free and therefore, is healthy to humans and the environment. The exceptional nutritional properties of the grain resulted in a gradual surge in its demand in the human food market especially for people with diabetes and celiac disease. It is essential to continue the genetic improvement of proso millet to meet its ever-increasing demand. Genetic improvement of proso millet in the United States, however, is impeded by the narrow genetic base in the germplasm and lack of extensive research on its genetics and breeding. There are lots of reports on ‘omics’ (genomics, transcriptomics, proteomics, metabolomics, and phenomics) of many common crops and the technologies are being extensively used in their genetic improvement. However, such studies are scarce in proso millet. The objective of this review article is to summarize available ‘omics’ reports of proso millet and discuss their relevance for its genetic improvement. Relatively more genomics and transcriptomics reports of proso millet are available but only two proteomics and metabolomics reports focusing on grain composition and no phenomics report are available. As more efficient, fast, and cheaper ‘omics’ technologies are available, it is imperative that global proso and other millets breeders and geneticists collaborate strongly for successful utilization of ‘milletomics’ for developing of noble proso millet varieties for future need of this climate-smart superfood grain.

Domesticated ~10,000 years ago in northern China, Proso millet (

Objective— Perturbations in hepatic lipid and very-low–density lipoprotein (VLDL) metabolism are involved in the pathogenesis of obesity and hepatic insulin resistance. The objective of this study is to delineate the mechanism of subdiaphragmatic vagotomy in preventing obesity, hyperlipidemia, and insulin resistance. Approach and Results— By subjecting the complete subdiaphragmatic vagotomized mice to various nutritional conditions and investigating hepatic de novo lipogenesis pathway, we found that complete disruption of subdiaphragmatic vagal signaling resulted in a significant decrease of circulating VLDL–triglyceride compared with the mice obtained sham procedure. Vagotomy further prevented overproduction of VLDL–triglyceride induced by an acute fat load and a high-fat diet–induced obesity, hyperlipidemia, hepatic steatosis, and glucose intolerance. Mechanistic studies revealed that plasma glucagon-like peptide-1 was significantly raised in the vagotomized mice, which was associated with significant reductions in mRNA and protein expression of SREBP-1c (sterol regulatory element-binding protein 1c), SCD-1 (stearoyl-CoA desaturase-1), and FASN (fatty acid synthase), as well as enhanced hepatic insulin sensitivity. In vitro, treating mouse primary hepatocytes with a glucagon-like peptide-1 receptor agonist, exendin-4, for 48 hours inhibited free fatty acid, palmitic acid treatment induced de novo lipid synthesis, and VLDL secretion from hepatocytes. Conclusions— Elevation of glucagon-like peptide-1 in vagotomized mice may prevent VLDL overproduction and insulin resistance induced by high-fat diet. These novel findings, for the first time, delineate an intrinsic gut–liver regulatory circuit that is mediated by glucagon-like peptide-1 in regulating hepatic energy metabolism.

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 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 activity 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 wild type 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 wild type 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.CREBH mediates inflammatory signaling to VLDL overproduction in metabolic stress. Activation of CREBH in inflammation enhances mRNA and protein expression of apoB. CREBH presents a potential novel therapeutic target for hyperlipoproteinemia.

Proso millet (Panicum miliaceum L.) is an annual cereal crop domesticated approximately 10,000 years ago in the semiarid regions of China. It is primarily grown in India, Nigeria, Niger, and China. Proso millet is used in Europe and North America as fodder and birdseed despite its highly nutritive and health-promoting benefits. Recently, the high content of different minerals and amino acids along with a low glycemic index and gluten-free property of the grains have attracted the industry and scientific communities. Proso millet has been used as a rotational crop in the winter wheat-fallow cropping system in the western Great Plains of the USA owing to its high water-use efficiency. This practice not only prevents the loss of organic matter from the no-till soil but also reduces weed and disease pressure. Regardless of the impeccable environmental and health benefits of proso millet, it remains as an under researched and underutilized crop. Plant breeders across the globe are trying to develop superior varieties using both classical and advanced breeding procedures. However, the lack of a genetic map and adequate genomic resources has slowed the crop improvement process. Proso millet germplasm representing a wide genetic diversity is conserved in gene banks maintained by several countries. The rapid growth in genomic research in the form of a linkage map development, novel molecular marker identification and availability of next-generation sequencing, together with high-throughput phenotyping promise to accelerate proso millet breeding. The development of proso millet cultivars which are high yielding, lodging and seed-shattering tolerant, direct combine-ready and nutrient enriched, would promote its increased cultivation, and use in the food industry.

A number of health-enhancing bioactive compounds have been identified in the seed of fenugreek, an annual legume. These compounds have been shown to exert multiple health beneficial effects on anti-obesity and type 2 diabetes. In this study, we characterized the molecular mechanisms of fenugreek seed in regulating lipid and lipoprotein metabolism and metabolic inflammatory stress. Two groups of hyperlipidemic mice induced by depletion of cAMP responsive element binding protein H were fed either a chow containing 2% fenugreek seed or vehicle control for 7 weeks. Q-RT-PCR and immunoblotting analysis demonstrated that fenugreek seed containing diet inhibited hepatic SREBP-1c activation and the subsequent de novo lipogenesis by enhancing expression of insulin-inducible gene-1 (Insig-1) and gene-2 (Insig-2). mRNA expression of PPARα and its target genes that were involved in fatty acid β-oxidation were also upregulated in the fenugreek seed treated-mice which was accompanied by significantly reduced hepatic lipid accumulation and VLDL secretion and improved endoplasmic reticulum (ER) stress. These actions ameliorated hepatic steatosis and systemic hyperlipidemia. Fenugreek seed further improved insulin sensitivity by upregulating expression of glucose transporters Glut-2 and Glut-4 and enhancing the activity of hepatic inulin signaling molecules, insulin receptor and AKT. In vitro, treating a rat hepatoma cell line, McA-RH7777, with trigonelline, a phytochemical compound in fenugreek seed, increased expression of Insig-2 which prevented the activation of SREBP-1c and the subsequent de novo lipid synthesis, resulting in less secretion of VLDL. Trigonelline treatment also attenuated ER stress induced by a free fatty acid, palmitic acid, indicated by the downregulation of GRP94/78 and reduced phosphorylation of JNK and eIF2α. This study unveiled a novel mechanism of the bioactive compound trigonelline in ameliorating metabolic inflammatory stress, hepatic steatosis, VLDL overproduction and insulin resistance via the mediation of Insig signaling. This evidence lands support for developing fenugreek seed as a nutraceutical supplement for the prevention and treatment of nutrient-surplus associated metabolic disorders.

Hyperlipidemia is a major complication of insulin-resistant states, such as obesity and type 2 diabetes, and contributes to an increased risk of cardiovascular disease. One key mechanism underlying the hyperlipidemia in metabolic syndrome is the overproduction of apolipoprotein B (apoB), the essential structural protein of the triglyceride-rich lipoproteins, such as very-low-density lipoproteins (VLDL) and chylomicrons. Currently, the underlying mechanisms for the overproduction of VLDL in metabolic syndrome are not fully understood. In this study, we demonstrated that the cAMP responsive element binding protein H (CREBH), an acute phase transcription factor, enhanced VLDL assembly and secretion by upregulating apoB expression, which contributed to hyperlipidemia associated metabolic inflammation. Specifically, we showed that over-expression of CREBH significantly induced mRNA and protein expression of apoB in McA-7777 cells. A luciferase assay further revealed that the presence of CREBH positively enhanced the activity of the apoB gene promoter. Genetic depletion of CREBH in mice resulted in significant reduction in expression of hepatic apoB mRNA. Moreover, challenging mice with a fat load via oral gavage upregulated VLDL secretion in wild type but not in the CREBH-null mice, suggesting the essential role of CREBH in apoB expression. Inflammatory cytokine TNFα treatment activated hepatic CREBH expression in wild type mice which subsequently enhanced hepatic apoB biosynthesis and VLDL secretion. This phenotype was not observed in CREBH-null mice. Metabolic inflammation induced by LPS or HFD also resulted in overproduction of apoB and hyperlipoproteinemia in wild type but not in CREBH-null mice. Conclusion: This study demonstrated that, for the first time, 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 transcription level and the subsequent VLDL biosynthesis in response to metabolic inflammation, and further provides novel mechanistic insight into the pathogenesis of hyperlipidemia in metabolic syndrome.

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.

Microspore culture of wheat generates completely homozygous (doubled haploid) plants in a single generation thereby reducing the time required for wheat variety development. Success of microspore culture in spring wheat is relatively higher than that in winter wheat. Cold mediated pretreatment was reported to improve response of microspore culture in wheat. The objective of the study was to determine and compare the influence of cold pretreatment on microspore culture in spring and winter wheat. Three spring (“Chris”, “Express”, and “Macon”) and three winter (“Anton”, “Antelope”, and “Camelot”) wheat cultivars were used. In cold pretreatment, excised anthers were incubated in solution B at 25˚C - 28˚C for 4 - 5 days followed by cold treatment at 4˚C for 5 days and were compared with the no-cold pretreatment at 25˚C - 28˚C for 4 - 5 days. Isolated microspores were cultured in induction medium (MMS4) at 27˚C - 28˚C for 25 - 30 days in the dark. Embryos (1 - 2 mm size) were transferred to regeneration medium (MMS5). Numbers of multicellular structures, transferable embryos and green plants were counted and data were used for analysis of variance using a generalized linear model. It was observed that cold pretreatment increased multicellular structures, transferable embryos and green plants in both spring and winter wheat. However, the degree of improvement was higher in spring wheat compared to winter wheat. The cultivars within spring and winter wheat responded differently. Development of embryos from pro-embryos was 4 - 5 folds lower in winter wheat than that in spring wheat, indicating requirement of a possibly different hormonal composition in induction medium for improving embryo induction in winter wheat. This report may provide future direction of research to improve microspore culture response in winter wheat.

Scope This study aims to characterize the effect of fenugreek (Trigonella foenum-graecum) seed and its phytoceutical trigonelline in antimetabolic inflammation and ameliorating overproduction of very low density lipoprotein (VLDL) in insulin resistance. Methods and results Two groups of genetic hyperlipidemic mice generated by depletion of cAMP responsive element binding protein H (CREBH) are fed either a chow containing 2% fenugreek seed or vehicle for 7 weeks. Q-RT-PCR and immunoblotting analysis demonstrated that fenugreek seed containing diet inhibits hepatic SREBP-1c activation and the subsequent de novo lipogenesis by enhancing expression of insulin-inducible gene-1 (Insig-1) and gene-2 (Insig-2). mRNA expression of PPARα and its target genes that are involved in fatty acid β-oxidation are also upregulated in the fenugreek seed fed-mice which is accompanied by significantly reduced hepatic lipid accumulation and VLDL secretion, improved endoplasmic reticulum (ER) stress, and ameliorated metabolic inflammation. These actions enhance insulin sensitivity and improve hyperlipidemia. In vitro, treating a rat hepatoma cell line, McA-RH7777 (McA), with trigonelline is able to recapitulate the results observed in vivo. Conclusions This study unveils a novel mechanism of fenugreek seed and trigonelline in countering hepatic VLDL overproduction and insulin resistance by enhancing the Insig signaling pathways and ameliorating metabolic inflammatory stress in the liver.

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 lipoprotein via the mediation of apolipoprotein B100 and apolipoprotein E, leading to the increased clearance of triglyceride-rich lipoprotein remnants, chylomicron remnants, and intermediate-density lipoproteins, from the circulation. Treatment with A muciniphila further improved hepatic endoplasmic reticulum stress and metabolic inflammation in CREBH-null mice. Conclusions— Increased colonization of the disease-protective gut bacteria A muciniphila protected the host from acute and chronic hyperlipidemia by enhancing the low-density lipoprotein receptor expression and alleviating hepatic endoplasmic reticulum stress and the inflammatory response in CREBH-null mice.