Background: Since the beginning of the COVID-19 pandemic, access to fresh food has been restricted, and people are spending more time inside and have limited their physical activity. However, more time at home may have resulted in some positive habits including an increase in cooking. The aim of this review was to assess dietary changes during the first lockdown. Themes and patterns were considered and associations with other lifestyle factors were assessed.Methods: Between June and July 2020, the PubMed, Google Scholar, and Science Direct databases were searched, and results were screened for eligibility based on title, abstract, and full text. The inclusion criteria of this search included: papers published (or in pre-print) in the year 2020; studies that investigated the impact of COVID-19 lockdown on diet; papers published in English. Exclusion criteria were as follows: papers examining dietary changes in those following a structured diet based on diagnosed conditions or dietetic advice; literature, systematic, or narrative studies reviewing previous research. Researchers agreed on the study characteristics for extraction from final papers.Results: Four thousand three hundred and twenty-two studies were originally considered with 23 final full-text papers included. Four themes were identified: dietary patterns, dietary habits (favorable), dietary habits (unfavorable), and other (includes physical activity levels, weight gain). A total of 10 studies reported an increase in the number of snacks consumed, while six studies found that participants increased their meal number and frequency during quarantine. Eleven studies reported favorable changes in dietary habits with an increase in fresh produce and home cooking and reductions in comfort food and alcohol consumption. However, nine studies found a reduction in fresh produce, with a further six reporting an increase in comfort foods including sweets, fried food, snack foods, and processed foods. Two studies reported an increase in alcohol consumption. In eight studies participants reported weight gain with seven studies reporting a reduction in physical exercise.Conclusion: The effect of COVID-19 lockdown both negatively and positively impacted dietary practices throughout Europe and globally, and negative diet habits were associated with other poor lifestyle outcomes including weight gain, mental health issues, and limited physical activity. Both in the short term and if sustained in the long term, these changes may have significant impacts on the health of the population.

OBJECTIVETo identify, localize, and determine M1/M2 polarization of epidydimal adipose tissue (eAT) macrophages (Φs) during high-fat diet (HFD)-induced obesity.RESEARCH DESIGN AND METHODSMale C57BL/6 mice were fed an HFD (60% fat kcal) or low-fat diet (LFD) (10% fat kcal) for 8 or 12 weeks. eATMΦs (F4/80+ cells) were characterized by in vivo fluorescent labeling, immunohistochemistry, fluorescence-activated cell sorting, and quantitative PCR.RESULTSRecruited interstitial macrophage galactose-type C-type lectin (MGL)1+/CD11c− and crown-like structure–associated MGL1−/CD11c+ and MGL1med/CD11c+ eATMΦs were identified after 8 weeks of HFD. MGL1med/CD11c+ cells comprised ∼65% of CD11c+ eATMΦs. CD11c+ eATMΦs expressed a mixed M1/M2 profile, with some M1 transcripts upregulated (IL-12p40 and IL-1β), others downregulated (iNOS, caspase-1, MCP-1, and CD86), and multiple M2 and matrix remodeling transcripts upregulated (arginase-1, IL-1Ra, MMP-12, ADAM8, VEGF, and Clec-7a). At HFD week 12, each eATMΦ subtype displayed an enhanced M2 phenotype as compared with HFD week 8. CD11c+ subtypes downregulated IL-1β and genes mediating antigen presentation (I-a, CD80) and upregulated the M2 hallmark Ym-1 and genes promoting oxidative metabolism (PGC-1α) and adipogenesis (MMP-2). MGL1med/CD11c+ eATMΦs upregulated additional M2 genes (IL-13, SPHK1, CD163, LYVE-1, and PPAR-α). MGL1med/CD11c+ ATMΦs expressing elevated PGC-1α, PPAR-α, and Ym-1 transcripts were selectively enriched in eAT of obese mice fed pioglitazone for 6 days, confirming the M2 features of the MGL1med/CD11c+ eATMΦ transcriptional profile and implicating PPAR activation in its elicitation.CONCLUSIONSThese results 1) redefine the phenotypic potential of CD11c+ eATMΦs and 2) suggest previously unappreciated phenotypic and functional commonality between murine and human ATMΦs in the development of obesity and its complications.

Adipose tissue (AT) inflammation promotes insulin resistance (IR) and other obesity complications. AT inflammation and IR are associated with oxidative stress, adipocyte death, and the scavenging of dead adipocytes by proinflammatory CD11c+ AT macrophages (ATMPhi). We tested the hypothesis that supplementation of an obesitogenic (high-fat) diet with whole blueberry (BB) powder protects against AT inflammation and IR. Male C57Bl/6j mice were maintained for 8 wk on 1 of 3 diets: low-fat (10% of energy) diet (LFD), high-fat (60% of energy) diet (HFD) or the HFD containing 4% (wt:wt) whole BB powder (1:1 Vaccinium ashei and V. corymbosum) (HFD+B). BB supplementation (2.7% of total energy) did not affect HFD-associated alterations in energy intake, metabolic rate, body weight, or adiposity. We observed an emerging pattern of gene expression in AT of HFD mice indicating a shift toward global upregulation of inflammatory genes (tumor necrosis factor-alpha, interleukin-6, monocyte chemoattractant protein 1, inducible nitric oxide synthase), increased M1-polarized ATMPhi (CD11c+), and increased oxidative stress (reduced glutathione peroxidase 3). This shift was attenuated or nonexistent in HFD+B-fed mice. Furthermore, mice fed the HFD+B were protected from IR and hyperglycemia coincident with reductions in adipocyte death. Salutary effects of BB on adipocyte physiology and ATMPhi gene expression may reflect the ability of BB anthocyanins to alter mitogen-activated protein kinase and nuclear factor-kappaB stress signaling pathways, which regulate cell fate and inflammatory genes. These results suggest that cytoprotective and antiinflammatory actions of dietary BB can provide metabolic benefits to combat obesity-associated pathology.

The role of adaptive immunity in obesity-associated adipose tissue (AT) inflammation and insulin resistance (IR) is controversial. We employed flow cytometry and quantitative PCR to assess T-cell recruitment and activation in epididymal AT (eAT) of C57BL/6 mice during 4-22 weeks of a high (60% energy) fat diet (HFD). By week 6, eAT mass and stromal vascular cell (SVC) number increased 3-fold in mice fed HFD, coincident with onset of IR. We observed no increase in the proportion of CD3+ SVCs or in gene expression of CD3, IFNγ, or regulated upon activation, normal T-cell expressed and secreted (RANTES) during the first 16 weeks of HFD. In contrast, CD11c+ macrophages (Mφ) were enriched 6-fold by week 8 (p < 0.01). SVC enrichment for T cells (predominantly CD4+ and CD8+) and elevated IFNγ and RANTES gene expression were detected by 20-22 weeks of HFD (p < 0.01), coincident with the resolution of eAT remodeling. HFD-induced T cell priming earlier in the obesity time course is suggested by (1) elevated (5-fold) IL-12p40 gene expression in eAT by week 12 (p ≤ 0.01) and (2) greater IFNγ secretion from PMA/ionophorestimulated eAT explants at week 6 (1 fold, p = 0.08) and week 12 (5 fold, p < 0.001). In summary, T cell enrichment and IFNγ gene induction occur subsequent to ATMφ recruitment, onset of IR and resolution of eAT remodeling. However, enhanced priming for IFNγ production suggests the contribution of CD4+ and/or CD8+ effectors to cell-mediated immune responses promoting HFDinduced AT inflammation and IR.

Inflammation associated with obesity may play a role in colorectal carcinogenesis, but the underlying mechanism remains unclear. This study investigated whether the Wnt pathway, an intracellular signaling cascade that plays a critical role in colorectal carcinogenesis, is activated by obesity-induced elevation of the inflammatory cytokine tumor necrosis factor-alpha (TNF-α). Animal studies were conducted on C57BL/6 mice, and obesity was induced by utilizing a high-fat diet (60% kcal). An inflammation-specific microarray was performed, and results were confirmed with real-time polymerase chain reaction. The array revealed that diet-induced obesity increased the expression of TNF-α in the colon by 72% (P=.004) and that of interleukin-18 by 41% (P=.023). The concentration of colonic TNF-α protein, determined by ex vivo culture assay, was nearly doubled in the obese animals (P=.002). The phosphorylation of glycogen synthase kinase 3 beta (GSK3β), an important intermediary inhibitor of Wnt signaling and a potential target of TNF-α, was quantitated by immunohistochemistry. The inactivated (phosphorylated) form of GSK3β was elevated in the colonic mucosa of obese mice (P<.02). Moreover, β-catenin, the key effector of canonical Wnt signaling, was elevated in the colons of obese mice (P<.05), as was the expression of a downstream target gene, c-myc (P<.05). These data demonstrate that diet-induced obesity produces an elevation in colonic TNF-α and instigates a number of alterations of key components within the Wnt signaling pathway that are protransformational in nature. Thus, these observations offer evidence for a biologically plausible avenue, the Wnt pathway, by which obesity increases the risk of colorectal cancer.

Menopause promotes central obesity, adipose tissue (AT) inflammation, and insulin resistance (IR). Both obesity and the loss of estrogen can activate innate and adaptive immune cells (macrophages, T cells). The respective impacts of weight gain and loss of ovarian hormones on AT inflammation and IR are poorly understood. Here we determined the temporal kinetics of fat accretion, AT inflammation, and IR over a 26-wk time course in ovariectomized (OVX) mice, a model of menopause. OVX and sham-operated (SHM) C57BL6 mice were fed a normal chow diet. Weight, body composition (magnetic resonance imaging), total and regional adiposity, activity, food intake, AT crown-like structures, biohumoral measures, and insulin sensitivity (insulin tolerance testing and homeostatic model assessment) were determined at wk 12, 20, and 26. Macrophages and T cells from perigonadal AT were immunophenotyped by fluorescence-associated cell sorting, and perigonadal adipose tissue (PGAT) gene expression was quantified by quantitative PCR. OVX mice (ϳ31 g) became fatter than SHM mice (ϳ26 g) by wk 12, but mice were equally insulin sensitive. PGAT of OVX mice contained more T cells but expressed higher levels of M2-M⌽ (arginase-1) and T cell-regulatory (cytotoxic T-lymphocyte antigen 4) genes. At wk 20, both OVX and SHM mice weighed approximately 35 g and were equally insulin sensitive with comparable amounts of PGAT and total body fat. OVX mice became less insulin sensitive than SHM mice by wk 26, coincident with the down-regulation of PGAT arginase-1 (Ϫ20-fold) and cytotoxic T-lymphocyte antigen 4 (2-fold) and up-regulation of M1/Th1 genes CD11c (ϩ2-fold), IL12p40 (ϩ2-fold), and interferon-␥ (ϩ78-fold). Ovarian hormone loss in mice induces PGAT inflammation and IR by mechanisms that can be uncoupled from OVX-induced obesity. (Endocrinology 153: 4266 -4277, 2012) C ompared with premenopausal women, postmenopausal women are at a much greater risk of developing metabolic diseases, such as cardiovascular disease and type 2 diabetes (1). Although the mechanism(s) linking the loss of ovarian hormone production to metabolic disturbances are not fully understood, weight gain and a redistribution of body fat toward a more android (i.e. central) distribution pattern are thought to play major roles (2).However, recent evidence suggests that the loss of ovarian hormone production is associated with symptoms of the metabolic syndrome, even in the absence of body weight changes (3), signifying that the loss of ovarian hormone production per se may disturb metabolic function. The aging process itself is associated with a decline in metabolic functioning; for example, insulin sensitivity declines with age in rodents and humans (4, 5). Although the mech-

Summary Genetic factors, specifically the VKORC1 and GGCX genes, have been shown to contribute to the interindividual variability in response to the vitamin K-antagonist, warfarin, which influences the dose required to achieve the desired anticoagulation response. These differences in warfarin sensitivity may be explained by differences in vitamin K status. Men and women (n = 416, 60–80 y), primarily of European descent, were genotyped for common polymorphisms in VKORC1 and GGCX. Cross-sectional associations exist between polymorphisms and biochemical markers of vitamin K [plasma phylloquinone, percent undercarboxylated osteocalcin (%ucOC)]. VKORC1 rs8050894 GG homozygotes had significantly higher cross-sectional measures of plasma phylloquinone than carriers of the CG or CC genotypes (plasma phylloquinone geometric means: GG 0.874±0.092 versus CG/CC 0.598± 0.044; p = 0.020), whereas carriers of VKORC1 rs7294 AA or AG had significantly lower plasma phylloquinone concentrations compared to GG homozygotes (plasma phyllo-quinone geometric means: 0.579±0.045 versus 0.762±0.057; p = 0.035). Cross-sectional analyses also revealed that heterozygous carriers of GGCX rs10187424 and rs7568458 had significantly lower %ucOC relative to either homozygous group. Polymorphisms in genes encoding enzymes involved in vitamin K metabolism may modulate plasma concentrations of phylloquionone and percent carboxylation of osteocalcin.

ObjectiveTo investigate the role of TNF-like weak inducer of apoptosis (TWEAK) in pathological adipose tissue (AT) remodeling and complications of obesity.Design and MethodsWild type (WT) and TWEAK knockout (KO) mice were fed normal diet (ND) or a high fat diet (HFD) for up to 17 weeks. Adipocyte death was induced using an established transgenic mouse model of inducible adipocyte apoptosis (FAT-ATTAC). Metabolic, biochemical, histologic and flow cytometric analyses were performed.ResultsTWEAK and its receptor, fibroblast growth factor-inducible molecule 14 (Fn14) were upregulated in gonadal (g)AT of WT mice after HFD week 4 and 24 h after induction of adipocyte apoptosis. Phenotypes of KO and WT mouse were indistinguishable through HFD week 8. However, at week 17 obese KO mice had ~30% larger gAT adipocytes and gAT mass than WT mice, coincident with reduced adipocyte death, enhanced insulin signaling, Th2/M2 immune skewing, fewer thick collagen fibers, and altered expression of extracellular matrix constituents and modulators that is consistent with reduced fibrosis and larger adipocytes. KO mice were less steatotic and became more insulin sensitive and glucose tolerant than WT mice after HFD week 12.ConclusionTWEAK constrains ‘healthy’ gAT expansion and promotes metabolic complications in severe obesity.