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Obesity in America is a public health crisis that will continue to impact the country at an individual, social, and economic level unless we address the disease with dietary modifications to reduce or prevent its development. Nutritional interventions designed for obesity treatment are constantly evolving. Berries, which are a rich source of polyphenols, have been suggested as a potential bioactive component, as they have been reported to have anti-obesity effects. Therefore, this review will provide an overview of epidemiological studies to introduce the idea of berries for health promotion. Studies conducted in both rodents and humans are summarized. This review includes an overview of the physiological responses associated with berry consumption, including the effects on the composition of the gut microbiota in humans and rodents, which demonstrate how berry consumption may provide a protective effect against obesity and its related comorbidities. However, these findings have yet to be translated into feasible, long-term nutrition intervention in humans. Future research into different berries and their components will identify effective, accessible functional food options that can augment nutritional interventions.

The prevalence of diet-induced obesity and type-2 diabetes remains a growing concern in the United States. As best management practices still include improved diet and physical activity, bioactive food components, contained within functional foods, show promise in curbing the cardiometabolic complications associated with excess weight and diabetes. Quinoa is an emerging candidate crop for its versatility in wide-ranging growing conditions as one approach to address food security, but it also contains several components that may serve as a dietary tool for post-industrial countries struggling with the health complications of caloric excess. Preliminary rodent feeding studies demonstrate that components within quinoa, namely, phytosteroids, phenolics, polysaccharides, and peptides, can prevent adiposity, dyslipidemia, and hyperglycemia. Mechanistic activity may involve reduced lipid absorption and adipogenesis, increased energy expenditure and glucose oxidation and corrected gut microbiota. Other intestinal actions may include blocked carbohydrate digestion with enhanced incretin signaling. Evidence in clinical trials is lacking and future research spanning cells to the clinic is needed to further elucidate the interesting preliminary reports reviewed here. Quinoa offers several unique attributes that could be harnessed to improve the dietary management of obesity and diabetes.

Berries and other anthocyanin-rich foods have demonstrated anti-obesity effects in rodents and humans. However, the bioactive components of these foods and their mechanisms of action are unclear. We conducted an intervention study with overweight and obese adults to isolate the effects of different berry components on bioenergetics. Subjects consumed whole mixed berries (high anthocyanin, high fiber), pressed berry juice (high anthocyanin, low fiber), berry-flavored gelatin (low anthocyanin, low fiber), or fiber-enriched gelatin (low anthocyanin, high fiber) for one week prior to a meal challenge with the same treatment food as the pre-feed period. Peripheral blood mononuclear cells were collected 2 h after the meal challenge, and cellular respiration was assessed via high-resolution respirometry. The high-anthocyanin, low-fiber treatment (berry juice) and the low-anthocyanin, high-fiber treatment (fiber-enriched gelatin) had opposite effects on cellular respiration. In the fasted state, berry juice resulted in the highest oxygen-consumption rate (OCR), while fiber-enriched gelatin resulted in the highest OCR in the fed state. Differences were observed in multiple respiration states (basal, state 3, state 4, uncoupled), with the greatest differences being between the pressed berry juice and the fiber-enriched gelatin. Different components of berries, specifically anthocyanins/flavonoids and fiber, appear to have differential effects on cellular respiration.

Evidence supports the beneficial effects of berries on glucoregulation, possibly related to flavonoid content, fiber content, or both. The purpose of this study was to assess the potential of mixed berries to improve insulin sensitivity and to identify the potential role of flavonoids and fiber. In a randomized cross-over trial with four treatment periods, overweight/obese men and women were fed a controlled 45% fat diet for one week prior to a meal-based glucose tolerance test. The same base diet was provided during each feeding period with the addition of one of four treatments: whole mixed berries, sugar matched mixed berry juice, sugar matched gelatin, and sugar/fiber matched gelatin. Subjects then completed a meal-based oral glucose tolerance test. Serum glucose, insulin and non-esterified fatty acids were not different between individual treatments. However, in a secondary analysis, the combined berry preparations resulted in a lower serum insulin area under the curve (difference of 0.15 &plusmn, 0.066 ln pmol min/mL, mean &plusmn, SE, p = 0.0228), compared to the combined gelatin treatments, while the difference for serum glucose did not quite meet statistical significance (difference of 0.17 &plusmn, 0.093 ln mg&middot, min/dL, mean &plusmn, SE, p = 0.0738). These results suggest the potential for mixed berry preparations to improve post-prandial insulin response.

Berries and other anthocyanin-rich treatments have prevented weight gain and adiposity in rodent models of diet-induced obesity. Their efficacy may be explained by modulation of energy substrate utilization. However, this effect has never been translated to humans. The objective of this study was to evaluate the effects of berry intake on energy substrate use and glucoregulation in volunteers consuming a high-fat diet. Twenty-seven overweight or obese men were enrolled in a randomized, placebo-controlled crossover study with two treatment periods. Subjects were fed an investigator controlled, high-fat (40% of energy from fat) diet which contained either 600 g/day blackberries (BB, 1500 mg/day flavonoids) or a calorie and carbohydrate matched amount of gelatin (GEL, flavonoid-free control) for seven days prior to a meal-based glucose tolerance test (MTT) in combination with a 24 h stay in a room-sized indirect calorimeter. The washout period that separated the treatment periods was also seven days. The BB treatment resulted in a significant reduction in average 24 h respiratory quotient (RQ) (0.810 vs. 0.817, BB vs. GEL, p = 0.040), indicating increased fat oxidation. RQ during the MTT was significantly lower with the BB treatment (0.84) compared to GEL control (0.85), p = 0.004. A 4 h time isolation during dinner showed similar treatment effects, where RQ was reduced and fat oxidation increased with BB (0.818 vs. 0.836, 28 vs. 25 g, respectively, BB vs. GEL treatments). The glucose AUC was not different between the BB and GEL treatments during the MTT (3488 vs. 4070 mg&middot, min/dL, respectively, p = 0.12). However, the insulin AUC was significantly lower with the BB compared to the GEL control (6485 vs. 8245 &micro, U&middot, min/mL, p = 0.0002), and HOMA-IR improved with BB (p = 0.0318). Blackberry consumption may promote increased fat oxidation and improved insulin sensitivity in overweight or obese males fed a high fat diet.

BACKGROUND Preclinical and epidemiologic studies suggest that garlic intake is inversely associated with the progression of cancer and cardiovascular disease. OBJECTIVE We designed a study to probe the mechanisms of garlic action in humans. METHODS We conducted a randomized crossover feeding trial in which 17 volunteers consumed a garlic-containing meal (100 g white bread, 15 g butter, and 5 g raw, crushed garlic) or a garlic-free control meal (100 g white bread and 15 g butter) after 10 d of consuming a controlled, garlic-free diet. Blood was collected before and 3 h after test meal consumption for gene expression analysis in whole blood. Illumina BeadArray was used to screen for genes of interest, followed by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) on selected genes. To augment human study findings, Mono Mac 6 cells were treated with a purified garlic extract (0.5 μL/mL), and mRNA was measured by qRT-PCR at 0, 3, 6, and 24 h. RESULTS The following 7 genes were found to be upregulated by garlic intake: aryl hydrocarbon receptor (AHR), aryl hydrocarbon receptor nuclear translocator (ARNT), hypoxia-inducible factor 1α (HIF1A), proto-oncogene c-Jun (JUN), nuclear factor of activated T cells (NFAT) activating protein with immunoreceptor tyrosine-based activation motif 1 (NFAM1), oncostatin M (OSM), and V-rel avian reticuloendotheliosis viral oncogene homolog (REL). Fold-increases in mRNA transcripts ranged from 1.6 (HIF1A) to 3.0 (NFAM1) (P < 0.05). The mRNA levels of 5 of the 7 genes that were upregulated in the human trial were also upregulated in cell culture at 3 and 6 h: AHR, HIF1A, JUN, OSM, and REL. Fold-increases in mRNA transcripts in cell culture ranged from 1.7 (HIF1A) to 12.1 (JUN) (P < 0.01). OSM protein was measured by ELISA and was significantly higher than the control at 3, 6, and 24 h (24 h: 19.5 ± 1.4 and 74.8 ± 1.4 pg/mL for control and garlic, respectively). OSM is a pleiotropic cytokine that inhibits several tumor cell lines in culture. CONCLUSION These data indicate that the bioactivity of garlic is multifaceted and includes activation of genes related to immunity, apoptosis, and xenobiotic metabolism in humans and Mono Mac 6 cells. This trial is registered at clinicaltrials.gov as NCT01293591.

Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent, proglucagon-derived gut hormone that shows promise for the treatment of short bowel syndrome (SBS). Our objective was to investigate how combination GLP-2 + enteral nutrients (EN) affects intestinal adaption in a rat model that mimics severe human SBS and requires parenteral nutrition (PN). Male Sprague-Dawley rats were assigned to one of five groups and maintained with PN for 18 days: total parenteral nutrition (TPN) alone, TPN + GLP-2 (100 μg·kg−1·day−1), PN + EN + GLP-2(7 days), PN + EN + GLP-2(18 days), and a nonsurgical oral reference group. Animals underwent massive distal bowel resection followed by jejunocolic anastomosis and placement of jugular catheters. Starting on postoperative day 4, rats in the EN groups were allowed ad libitum access to EN. Groups provided PN + EN + GLP-2 had their rate of PN reduced by 0.25 ml/day starting on postoperative day 6. Groups provided PN + EN + GLP-2 demonstrated significantly greater body weight gain with similar energy intake and a safe 80% reduction in PN compared with TPN ± GLP-2. Groups provided PN + EN + GLP-2 for 7 or 18 days showed similar body weight gain, residual jejunal length, and digestive capacity. Groups provided PN + EN + GLP-2 showed increased jejunal GLP-2 receptor (GLP-2R), insulin-like growth factor-I (IGF-I), and IGF-binding protein-5 (IGFBP-5) expression. Treatment with TPN + GLP-2 demonstrated increased jejunal expression of epidermal growth factor. Cessation of GLP-2 after 7 days with continued EN sustained the majority of intestinal adaption and significantly increased expression of colonic proglucagon compared with PN + EN + GLP-2 for 18 days, and increased plasma GLP-2 concentrations compared with TPN alone. In summary, EN potentiate the intestinotrophic actions of GLP-2 by improving body weight gain allowing for a safe 80% reduction in PN with increased jejunal expression of GLP-2R, IGF-I, and IGFBP-5 following distal bowel resection in the rat.

Phenylketonuria (PKU) is caused by a mutation in the phenylalanine (phe) hydroxylase gene and requires a low-phe diet plus amino acid (AA) formula to prevent cognitive impairment. Glycomacropeptide (GMP) contains minimal phe and provides a palatable alternative to AA formula. Our objective was to compare growth, body composition, and energy balance in Pahenu2 (PKU) and wild-type mice fed low-phe GMP, low-phe AA, or high-phe casein diets from 3–23 wk of age. The 2 × 2 × 3 design included main effects of genotype, sex, and diet. Fat and lean mass were assessed by dual-energy X-ray absorptiometry, and acute energy balance was assessed by indirect calorimetry. PKU mice showed growth and lean mass similar to wild-type littermates fed the GMP or AA diets; however, they exhibited a 3–15% increase in energy expenditure, as reflected in oxygen consumption, and a 3–30% increase in food intake. The GMP diet significantly reduced energy expenditure, food intake, and plasma phe concentration in PKU mice compared with the casein diet. The high-phe casein diet or the low-phe AA diet induced metabolic stress in PKU mice, as reflected in increased energy expenditure and intake of food and water, increased renal and spleen mass, and elevated plasma cytokine concentrations consistent with systemic inflammation. The low-phe GMP diet significantly attenuated these adverse effects. Moreover, total fat mass, %body fat, and the respiratory exchange ratio (CO2 produced/O2 consumed) were significantly lower in PKU mice fed GMP compared with AA diets. In summary, GMP provides a physiological source of low-phe dietary protein that promotes growth and attenuates the metabolic stress induced by a high-phe casein or low-phe AA diet in PKU mice.

Glucagon-like peptide-2 (GLP-2) action is dependent on intestinal expression of IGF-I, and IGF-I action is modulated by IGF binding proteins (IGFBP). Our objective was to evaluate whether the intestinal response to GLP-2 or IGF-I is dependent on expression of IGFBP-3 and -5. Male, adult mice in six treatment groups, three wild-type (WT) and three double IGFBP-3/-5 knockout (KO), received twice daily intraperitoneal injections of GLP-2 (0.5 μg/g body wt), IGF-I (4 μg/g body wt), or PBS (vehicle) for 7 days. IGFBP-3/-5 KO mice showed a phenotype of lower plasma IGF-I concentration, but greater body weight and relative mass of visceral organs, compared with WT mice ( P < 0.001). WT mice showed jejunal growth with either IGF-I or GLP-2 treatment. In KO mice, IGF-I did not stimulate jejunal growth, crypt mitosis, sucrase activity, and IGF-I receptor (IGF-IR) expression, suggesting that the intestinotrophic actions of IGF-I are dependent on expression of IGFBP-3 and -5. In KO mice, GLP-2 induced significant increases in jejunal mucosal cellularity, crypt mitosis, villus height, and crypt depth that was associated with increased expression of the ErbB ligand epiregulin and decreased expression of IGF-I and IGF-IR. This suggests that in KO mice, GLP-2 action in jejunal mucosa is independent of the IGF-I system and linked with ErbB ligands. In summary, the intestinotrophic actions of IGF-I, but not GLP-2, in mucosa are dependent on IGFBP-3 and -5. These findings support the role of multiple downstream mediators for the mucosal growth induced by GLP-2.